제33차춘계학술대회및 제7차국제심포지엄 · 10：20∼10：30 persistent...

pISSN 2093-940XeISSN 2233-4718

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Official Journal of Korean College of Rheumatology

Journal of Rheumatic DiseasesVol. 20, Suppl. 1, May, 2013

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일자 I 2013년 5월 10일(금)~11일(토)

장소 I 세종대학교광개토관컨벤션센터(컨벤션홀)

대한류마티스학회

제33차춘계학술대회및제7차국제심포지엄

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JOURNAL OF RHEUMATIC DISEASESVol. 20, Suppl. 1, May, 2013

PROGRAM

일 자: 2013년 5월 10일(금)∼11일(토)장 소: 세종대학교 광개토관 컨벤션센터(컨벤션홀)

2013년 5월 10일(금)

08：30∼09：00 Registration

08：50∼09：00 Opening Remarks 회 장 김 동 수

Welcome Address 이사장 유 대 현

09：00∼10：30 International Symposium (Convention Hall A, B, 지하 2층)

Chair：Dae-Hyun Yoo (Hanyang Univ., Korea), Gun-Il Im (Dongguk Univ., Korea)

09：00∼09：40 The Anti-angiogenic, Anti-tumor and Anti-osteoclast Functions of Cartilage Linda J. Sandell

09：40∼10：05 Hypoxia-inducible Factor-2α Regulation of Osteoarthritis and Rheumatoid Arthritis Jang-Soo Chun

10：05∼10：30 DAMP Signaling in Osteoarthritis Hyun Ah Kim

10：30∼11：00 Coffee Break and Poster Viewing

11：00∼11：40 Invited Lecture I (Convention Hall A, B, 지하 2층)

Chair：Eun-Mi Koh (Sungkyunkwan Univ., Korea)

Systemic Lupus: Cells, Signals and Cytokines Philip Cohen

11：40∼12：00 Korean Biologics Registry 사업 소개 임상연구위원회

12：00∼13：30 Luncheon Symposium and Lunch Break (Convention Hall A, B, 지하 2층)

좌장：박 원(인하의대)

ii

13：30∼14：10 Free Paper Session (1-1)：RA - Pathogenesis (I) (Convention Hall A, 지하 2층)

좌장：이수곤(연세의대)ㆍ박성환(가톨릭의대)

13：30∼13：40 Global Metabolite Profiling of Synovial Fluids from Different Forms of Inflammatory

Arthritis for the Identification of Putative Biomarker in Rheumatoid Arthritis 황지원

13：40∼13：50 Discriminative Metabolite Profiling of Synovial Fluid in Rheumatoid Arthritis

Compared to Osteoarthritis 황지원

13：50∼14：00 MRP8 Promotes Th17 Differentiation Via Upregulation of IL-6 Production

by Fibroblast-like Synoviocytes in Rheumatoid Arthritis 정승민

14：00∼14：10 Coenzyme Q10 Suppresses Autoimmune Arthritis Via Regulation of Th17/Treg Cells 이주하

14：10∼14：50 Free Paper Session (1-2)：Osteoclasts and Joint Destruction (Convention Hall A, 지하 2층)

좌장：강영모(경북의대)ㆍ지종대(고려의대)

14：10∼14：20 Dysregulated Osteoclastogenesis is Related to Natural Killer

T Cell Dysfunction in Rheumatoid Arthritis 진혜미

14：20∼14：30 Tubastatin A, A Selective HDAC6 Inhibitor, Suppresses Synovial Inflammation

and Joint Destruction in a Collagen Antibody-induced Arthritis Mouse Model 이재준

14：30∼14：40 Red Ginseng Extract Regulates Regulatory T Cell and Th17 Cell,

and Inhibits Osteoclastogenesis in Autoimmune Arthritis 이재호

14：40∼14：50 Anthocyanins Extracted from Black Soybean Seed Coat Suppress Autoimmune

Arthritis and Prevent Osteoclast Formation 서영선

13：30∼14：10 Invited Lecture II (Convention Hall B, 지하 2층)

Chair：Seung Cheol Shim (Chungnam National Univ., Korea)

The Utility of Ultrasound in the Detection and Monitoring of Synovitis

and Disease Activity in Rheumatoid Arthritis Peter Mandl

14：10∼14：50 Free Paper Session (2-1)：Spondylarthropathies (Convention Hall B, 지하 2층)

좌장：백한주(가천의대)ㆍ차훈석(성균관의대)

14：10∼14：20 Clinical Characteristics of Late-onset Ankylosing Spondylitis 김광열

14：20∼14：30 Factors and Outcomes of Diagnostic Delay in Korean Patients with Spondyloarthritis 서미령

14：30∼14：40 Phenotype Difference in Familial Ankylosing Spondylitis (AS) Compared to Sporadic AS 김혜원

14：40∼14：50 The Reliability and Validity of a Korean Translation of the ASAS Health Index

in Korean Patients with Ankylosing Spondylitis 김태종

iii

13：30∼14：10 Free Paper Session (3-1)：Fibromyalgia and Miscellaneous (Conference 1, 지하 1층)

좌장：이신석(전남의대)ㆍ강성욱(충남의대)

13：30∼13：40 Relationship Between Body Mass Index, Fat Mass and Muscle Mass

with Musculoskeletal Pain in Community Residents 유종진

13：40∼13：50 The Symptom Severity of Fibromyalgia is Associated with Socioeconomic Status,

not with Obesity in Korean Patients with Fibromyalgia 박동진

13：50∼14：00 The Significance of Ectopic Germinal Center in Minor Salivary Gland of Patients

with Sjögren’s Syndrome 이경은

14：00∼14：10 The Ratio and Clinical Characteristics of IgG4-related Retroperitoneal Fibrosis Patients

Among Idiopathic RPF Patients 구본산

14：10∼14：50 Free Paper Session (3-2)：Chondrocytes and Osteoarthritis (Conference 1, 지하 1층)

좌장：이광현(한양의대)ㆍ김현아(한림의대)

14：10∼14：20 Fibronectin Fragment Induces Procatabolic Effects through TLR-2 and not TLR-4

Signaling Pathway in Human Articular Chondrocytes 천은정

14：20∼14：30 Association Between Body Composition and Knee Pain and Radiographic Knee

Osteoarthritis in Community Residents in Korea 김인제

14：30∼14：40 MicroRNA-558 Regulates the Expression of Cyclooxygenase-2 and IL-1β-induced

Catabolic Effects in Human Articular Chondrocytes 김현아

14：40∼14：50 Metabolically Abnormal but Normal Weight, Metabolically Healthy Obesity,

and Knee Osteoarthritis: A Cross-sectional Study in Korean Women 이성근

14：50∼15：20 Coffee Break

15：20∼16：00 Free Paper Session (2-2)：SLE -Pathogenesis (Convention Hall B, 지하 2층)

좌장：배상철(한양의대)ㆍ서창희(아주의대)

15：20∼15：30 Mucosal-associated Invariant T Cell Deficiency in Systemic Lupus Erythematosus 조영난

15：30∼15：40 Human Adipose Derived Mesenchymal Stem Cells Induce the Expansion

of Regulatory B Cells and Ameliorate Autoimmunity in a Murine Model

of Systemic Lupus Erythematosus 곽승기

15：40∼15：50 CD40 Activated Human CD27-CD38Int Pre-naive B Cells Modulate CD4+

T Cell Activation Via IL-10 Production 이지수

15：50∼16：00 Delta Neutrophil Index as a Useful Marker for the Differential Diagnosis Between Flare

and Infection in Febrile Patients with Systemic Lupus Erythematosus 하유정

iv

16：00∼16：40 Free Paper Session (2-3)：Drug Therapies (Convention Hall B, 지하 2층)

좌장：송관규(고려의대)ㆍ류완희(전북의대)

16：00∼16：10 The Concomitant Use of Meloxicam and Methotrexate did not Increase the Risk

of Silent Kidney or Liver Damage in Patients with Rheumatoid Arthritis 박희진

16：10∼16：20 Blood B Cell Counts as Predictor of Early Clinical Response after Rituximab

in Patients with Rheumatoid Arthritis 김유재

16：20∼16：30 Efficacy and Safety of Tacrolimus in Active Rheumatoid Arthritis Patients Shown

Unsuccessful Response Against Methotrexate: Non-comparative, Single Arm,

Multi-center, Phase 4 Study 이원석

16：30∼16：40 The Effect of Uric Acid Lowering Therapy (ULT) in Preventing Comorbidity

of Gout and Acute Gout Attack, A Retrospective Study 주고운

15：20∼16：00 Free Paper Session (3-3)：Health Services Research (Conference 1, 지하 1층)

좌장：정원태(동아의대)ㆍ이영호(고려의대)

15：20∼15：30 한국의 종합 병원 외래에서 항-종양괴사인자 α(anti-TNFα) 치료에 한

보험 여 기 을 충족하는 류마티스 염 환자의 비율：

다기 , 비 재 , 찰 연구 김 담

15：30∼15：40 Systemic Review: Agreement Between Tuberculin Skin Test (TST) and

Interferon-gamma Release Assay (IGRA) Blood Test for Latent TB Screening

Among Patients with Rheumatic Diseases 성윤경

15：40∼15：50 Current Status of Ultrasound Use in Rheumatology in Korea 강태영

15：50∼16：00 Predictors of Indeterminate INF-γ Release Assay in Rheumatic Diseases 정현주

16：00∼16：40 Free Paper Session (3-4)：RA-Clinical Aspects (Conference 1, 지하 1층)

좌장：이상헌(건국의대)ㆍ이성원(동아의대)

16：00∼16：10 Inflammatory Burden Predicts Carotid Plaque Progression

and Clinical Cardiovascular Disease in Rheumatoid Arthritis:

the Second Year KARRA Cohort Studyarthritis 임철현

16：10∼16：20 류마티스 염 환자에서 고 압이 심 계 험도와 질병경과에 미치는 향 최찬범

16：20∼16：30 Longitudinal Radiographic Analysis of Rheumatoid Wrist: Minimum 7 Year Follow-up 이창훈

16：30∼16：40 Elevated Serum Resistin Levels in Rheumatoid Arthritis with Periodontitis 최병용

16：40∼17：25 대한류마티스학회 젊은연구자상 수상 및 수상자 강연(Convention Hall B, 지하 2층)

대한류마티스학회 학술상 수상 및 수상자 강연

17：25∼17：50 총 회 총무이사 차 훈 석

17：50∼18：00 Closing Remarks 회 장 김 동 수

18：00∼ Dinner (Convention Hall A, 지하 2층)

v

2013년 5월 11일(토)

08：00∼08：20 Registration

08：20∼08：30 Introduction (Convention Hall A, 지하 2층) 회장 김 동 수

08：30∼10：00 Symposium: 한국인 류마티스관절염 (Convention Hall A, 지하 2층)

좌장：김동수(연세의대)ㆍ이찬희(국민건강보험공단 일산병원)

08：30∼08：35 류마티스 염 임상연구센터 소개 배상철

08：35∼08：55 류마티스 염 다기 코호트 구축과 임상약물역학연구 배상철

08：55∼09：10 류마티스 염 진단 후에 한 측지표 연구 이수곤

09：10∼09：25 류마티스 염 치료근거 확립을 한 연구 자주도 임상시험 고안 수행 송영욱

09：25∼09：40 류마티스 염 약물치료의 경제성 평가 이의경

09：40∼09：55 한국형 류마티스 염 표 진료지침과 개발 박성환

09：55∼10：00 Discussion

08：20∼08：30 Introduction (Convention Hall B, 지하 2층) 이사장 유 대 현

08：30∼10：00 Special Lectures (귀국보고) (Convention Hall B, 지하 2층)

좌장：유빈(울산의대)ㆍ양형인(경희의대)

08：30∼08：50 Dual Phosphoinositide 3-kinase (PI3K)-delta/gamma Inhibitor

in Animal Models of Rheumatoid Arthritis 김해림

08：50∼09：10 Lymph Node Stromal Cells and Lymphotoxin in Immune Tolerance 박경수

09：10∼09：30 Health Status and Outcomes in RA: Cross-national Comparison Study

between South Korea and US 성윤경

09：30∼09：50 Role and Its Autoantibody in Ankylosing Spondylitis 김용길

09：50∼10：00 Discussion

10：00∼10：40 Free Paper Session (1-3)：RA-Pathogenesis (II) (Convention Hall A, 지하 2층)

좌장：최정윤(대구가톨릭의대)ㆍ이윤종(서울의대)

10：00∼10：10 Smoking, the HLA-DRB1 Shared Epitope and ACPA Fine-specificity in Koreans

with Rheumatoid Arthritis: Evidence for more than One Pathogenic Pathway 방소영

10：10∼10：20 DICAM Inhibits Angiogenesis Via Suppression of AKT and p38 MAP Kinase Signaling 한승우

10：20∼10：30 Interleukin-33 Acts as a Transcriptional Repressor and Extracellular Cytokine

in Fibroblast-like Synoviocytes in Patients with Rheumatoid Arthritis 이은주

10：30∼10：40 Serum Dickkopf-1/R Spondin-1 Ratio is a Novel Biomarker for Wnt Signaling Status

in Patients with Rheumatoid Arthritis 최병용

vi

10：00∼10：40 Free Paper Session (2-4)：SLE-Clinical Aspects (Convention Hall B, 지하 2층)

좌장：이지수(이화의대)ㆍ이혜순(한양의대)

10：00∼10：10 Hydroxychloroquine 망막병증의 선별검사 결과 김상진

10：10∼10：20 Comparison of Mycophenolate Mofetil and Intravenous Cyclophosphamide

as Induction Therapy in Korean Patients with Lupus Nephritis 박동진

10：20∼10：30 Persistent Dyslipidemia is a Risk Factor of Progression to Chronic Kidney Disease

in Patients with Lupus Nephritis 박동진

10：30∼10：40 The Assessment of Psychological Stress Using Saliva in SLE 정주양

10：00∼10：40 Free Paper Session (3-5)：Myositis and AOSD (Conference 1, 지하 1층)

좌장：전재범(한양의대)ㆍ이은봉(서울의대)

10：00∼10：10 The Potential Role of Mast Cells in the C-protein Induced Myositis Model 신기철

10：10∼10：20 The Effect of CXCL10 Blockade in C Protein-induced Myositis 김진현

10：20∼10：30 Delta Neutrophil Index as an Early Marker for Differential Diagnosis of

Adult-onset Still’s Disease and Sepsis 박희진

10：30∼10：40 Biomarkers as Reflecting Disease Activity in Korean Patients

with Adult Onset Still’s Disease 김진주

10：40∼11：10 Coffee Break and Poster Viewing

11：10∼11：50 Free Paper Session (1-4)：TNF Inhibitor-related Issues (Convention Hall A, 지하 2층)

좌장：송영욱(서울의대)ㆍ김진석(제주의대)

11：10∼11：20 Mortality in Patients with Rheumatoid Arthritis-associated Interstitial Lung Disease Treated

with an Anti-tumor Necrosis Factor Agent 구본산

11：20∼11：30 Drug Survival Rates of Antitumor Necrosis Factor Therapies in Patients

with Rheumatoid Arthritis and Ankylosing Spondylitis 이정원

11：30∼11：40 강직성 척추염에서 종양괴사인자 차단제의 도량학 효과에 한 측 인자 남언정

11：40∼11：50 TNF 길항제가 응이 되는 류마티스 염 환자들의 임상양상 손경민

11：10∼11：50 Free Paper Session (2-5)：RA-Pathogenesis (III) (Convention Hall B, 지하 2층)

좌장：박성환(가톨릭의대)ㆍ박용범(연세의대)

11：10∼11：20 Foxp3-expressing Regulatory B Cells Inhibit Autoimmune Arthritis in a Mouse Model 민준기

11：20∼11：30 Treatment of Collagen-induced Arthritis Using Immune Modulatory Properties

of Human Mesenchymal Stem Cells 박규형

vii

11：30∼11：40 Regulation of Apoptosis and Inflammatory Responses by IGFBP-3 in Fibroblast-like

Synoviocytes and Experimental Animal Models of Rheumatoid Arthritis 이화숙

11：40∼11：50 CD70 Expressing CD4 T Cells Produce IFN-γ and IL-17 in Rheumatoid Arthritis 박진균

11：10∼11：40 Free Paper Session (3-6)：Epidemiology (Conference 1, 지하 1층)

좌장：김중곤(서울의대)ㆍ송정수(중앙의대)

11：10∼11：20 Prevalence of and Risk Factors for Spine OA and its Association

with Low Back Pain Among Community Residents in Korea 이성연

11：20∼11：30 Prevalence and Incidence of Osteonecrosis in Patients

with Systemic Lupus Erythematosus 주영빈

11：30∼11：40 Prevalence and Incidence of Systemic Lupus Erythematosus in South Korea 심지선

11：50∼12：30 Invited lecture III (Convention Hall B, 지하 2층)

Chair：Ho-Youn Kim (Konkuk Univ., Korea)

Innate Immune Responses and Gut Homeostasis Kiyoshi Takeda

12：30∼12：40 우수구연상 및 우수포스터상 수상(Convention Hall B, 지하 2층)

12：40∼13：50 Luncheon Symposium and Lunch Break (Convention Hall B, 지하 2층)

좌장：이충기(영남의대)

13：50∼14：00 Closing Remarks 회장 김 동 수

viii

연구회 PROGRAM

일 자: 2013년 5월 11일(토)장 소: 세종대학교 광개토관 컨벤션센터

활막염연구회

사회： 경상의대, 활막염 연구회 총무 이 상 일

10：00∼10：10 등 록

10：10∼10：20 개회사 충남의대, 활막염 연구회 회장 심 승 철

10：20∼10：30 전임 임원진 감사패 전달

10：30∼12：00 Special Lectures I (Conference 3, 지하 1층)

좌장：이수곤(연세의대)ㆍ심승철(충남의대)

10：30∼11：00 Intracellular Heparin Alleviates T Cell-mediated Inflammatory Arthritis

by Inhibiting RhoA-dependent Transcellular Diapedesis 강영모

11：00∼11：30 Autophagy: An Innate Immune Effector Against Mycobacteria 조은경

11：30∼12：00 Mycobacterium Tuberculosis Heparin-binding Hemagglutinin and HspX,

A Novel TLR4 Agonist, Induces Dendritic Cells-based Immunotherapy

Via Drives Th1 Immune Response 박영민

12：00∼12：30 Oral Presentation I (Conference 3, 지하 1층)

좌장：양형인(경희의대)ㆍ김태종(전남의대)

12：00∼12：15 Dysfunction of Natural Killer T Cells in Patients with Active

Mycobacterium Tuberculosis Infection 조영난

12：15∼12：30 The Disparate Capacity for Differentiation and Immunosuppression

of Mesenchymal Stem Cells of the Patients with Rheumatoid Arthritis

According to the Disease Stage 김현옥

12：40∼13：50 Luncheon Symposium and Lunch Break (Convention Hall B, 지하 2층)

좌장：이충기(영남의대)

14：00∼14：20 어떻게 실험을 시작할 것인가? (활막염 연구회 홈페이지 활용 Tips) (Conference 3, 지하 1층)

어떻게 실험을 시작할 것인가? (활막염 연구회 홈페이지 활용 Tips) 이명수

ix

14：20∼15：20 Special Lectures II (Conference 3, 지하 1층)

좌장：김호연(건국의대)ㆍ김현아(한림의대)

14：20∼14：50 Techniques in Human T Cell Study: Application for Rheumatology 신의철

14：50∼15：20 Genetic Predispositions to Rheumatoid Arthritis and Lupus 강창원

15：20∼16：05 Oral Presentation II (Conference 3, 지하 1층)

좌장：박용욱(전남의대)ㆍ이상일(경상의대)

15：20∼15：35 Leukocyte-specific Protein 1 (LSP-1) is a Negative Regulator

of T Cell Migration 황성혜

15：35∼15：50 pH-responsive Nanoparticles Carrying Methotrexate

for Treatment of Inflammatory Arthritis 성시진

15：50∼16：05 Effects of Oleanolic Acid Acetate on Osteoclast Differentiation and Bone Resorption 이창훈

16：05∼16：10 맺음말 충남의대, 활막염 연구회 회장 심 승 철

류마티즘골대사연구회

13：30∼14：00 접수 및 등록

14：00∼14：10 개회사 인하의대, 류미티즘골대사연구회 회장 박 원

14：10∼15：00 제1부(Convention Hall A, 지하 2층)

좌장：박 원(인하의대)

Runx2 Stability and Transcriptional Activity is Regulated by Pin1 류현모

15：00∼16：10 제2부(Convention Hall A, 지하 2층)

좌장：서창희(아주의대)

15：00∼15：35 Oxidative Stress and Osteoporosis 민준기

15：35∼16：10 Regulatory T Cells in HLA B27 Transgenic Rats 권성렬

x

통풍연구회

14：00∼16：00 제1부 통풍(Convention Hall B, 지하 2층)

좌장：전재범(한양의대)

14：00∼14：30 환자가 가르쳐 주는 통풍: 증례 김현옥

14：30∼15：00 한국인에서 Sugar-sweetened Soft Drink와 요산의 계 김성규

15：00∼15：30 2012년 미국류마티스학회의 통풍치료 가이드라인 송정수

15：30∼16：00 통풍의 진료지침개발을 한 제안 김현아

16：00∼17：00 제2부 가성통풍(Convention Hall B, 지하 2층)

좌장：박성환(가톨릭의대)

16：00∼16：20 부갑상선기능항진증에 의한 가성통풍: 증례 전재범

16：20∼17：00 CPPD 질환의 용어, 진단 치료에 한 유럽류마티스학회의 권고사항 전찬홍

척추관절염연구회

13：30∼14：00 접수 및 등록

14：00∼14：10 개회사 한양의대, 척추관절염연구회 회장 김 태 환

14：00∼15：00 제1부(Conference 1, 지하 1층)

좌장：김태환 (한양의대)

14：10∼14：35 강직성척추염은 유 질환인가? 심승철

14：35∼15：00 건선 염, 정말드문가?-역학, 진단, 치료 백한주

15：10∼16：00 제2부(Conference 1, 지하 1층)

좌장：백한주(가천의대)

15：10∼15：35 척추 염의 MRI 유용성, 발병기 이해와 조기진단 신기철

15：35∼16：00 강직성척추염의 치료 리 김태종

xi

JOURNAL OF RHEUMATIC DISEASESVol. 20, Suppl. 1, May, 2013

목 차

2013년 5월 10일(금)

International Symposium (Convention Hall A, B, 지하 2층)

　1. The Anti-angiogenic, Anti-tumor and Anti-osteoclast Functions of Cartilage

Linda J. Sandell ······················································································································································· S3

　2. Hypoxia-inducible Factor-2α Regulation of Osteoarthritis and Rheumatoid Arthritis

Jang-Soo Chun ······················································································································································· S4

　3. DAMP Signaling in Osteoarthritis

Hyun Ah Kim ···························································································································································· S5

Invited Lecture I (Convention Hall A, B, 지하 2층)

　1. Systemic Lupus - Cells, Signals, and Cytokines

Philip Cohen ····························································································································································· S9

Invited Lecture II (Convention Hall B, 지하 2층)

　1. The Utility of Ultrasound in the Detection and Monitoring of Synovitis

and Disease Activity in Rheumatoid Arthritis

Peter Mandl ······························································································································································ S13

Free Paper Session (1-1)：RA - Pathogenesis (I) (Convention Hall A, 지하 2층)

　1. Global Metabolite Profiling of Synovial Fluids from Different Forms of Inflammatory Arthritis

for the Identification of Putative Biomarker in Rheumatoid Arthritis

Jiwon Hwang, Sooah Kim, Jaejoon Lee, Joong Kyong Ahn, Eun-Mi Koh,

Kyoung Heon Kim, Hoon-Suk Cha ······················································································································ S17

　2. Discriminative Metabolite Profiling of Synovial Fluid in Rheumatoid Arthritis Compared to Osteoarthritis

Jiwon Hwang, Sooah Kim, Jaejoon Lee, Joong Kyong Ahn, Eun-Mi Koh,

Kyoung Heon Kim, Hoon-Suk Cha ······················································································································ S18

　3. MRP8 Promotes Th17 Differentiation Via Upregulation of IL-6 Production by Fibroblast-like

Synoviocytes in Rheumatoid Arthritis

정승민ㆍ이재호ㆍ서영선ㆍ고정희ㆍ이주하ㆍ곽승기ㆍ박경수ㆍ박성환 ···························································· S19

　4. Coenzyme Q10 Suppresses Autoimmune Arthritis Via Regulation of Th17/Treg Cells

이주하ㆍ전주연ㆍ변재경ㆍ김은경ㆍ곽승기ㆍ박경수ㆍ조미라ㆍ박성환 ···························································· S20

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Free Paper Session (1-2)：Osteoarthritis and Joint Destruction (Convention Hall A, 지하 2층)

　1. Dysregulated Osteoclastogenesis is Related to Natural Killer T Cell Dysfunction in Rheumatoid Arthritis

진혜미ㆍ조영난ㆍ김문주ㆍ정현주ㆍ김재이ㆍ이정원ㆍ이경은ㆍ박동진ㆍ김태종ㆍ이신석

기승정ㆍ김낙성ㆍ유대현ㆍ박용욱 ·························································································································· S21

　2. Tubastatin A, A Selective HDAC6 Inhibitor, Suppresses Synovial Inflammation and Joint

Destruction in a Collagen Antibody-induced Arthritis Mouse Model

Jaejoon Lee, Eun Chung Hong, In Young Kim, Hyemin Jeong, Jiwon Hwang, Hyungjin Kim,

Eun-Kyung Bae, Joong Kyong Ahn, Hoon-Suk Cha, Eun-Mi Koh ······························································· S22

　3. Red Ginseng Extract Regulates Regulatory T Cell and Th17 Cell, and Inhibits Osteoclastogenesis

in Autoimmune Arthritis

Jae Ho Lee, Jung Hee Koh, Young Sun Suh, Seung-Min Jung, Jennifer Lee, Mi-La Cho,

Seung-Ki Kwok, Kyung-Su Park, Sung-Hwan Park ······················································································ S23

　4. Anthocyanins Extracted from Black Soybean Seed Coat Suppress Autoimmune

Arthritis and Prevent Osteoclast Formation

Young Sun Suh, Dong-Gun Lee, Jung-Won Woo, Seung-Ye Baek, Sung-Min Kim,

Seung-Ki Kwok, Sung Hwan Park ······················································································································· S24

Free Paper Session (2-1)：Spondylarthropathies (Convention Hall B, 지하 2층)

　1. Clinical Characteristics of Late-onset Ankylosing Spondylitis

김광열ㆍ송 란ㆍ홍승재ㆍ양형인ㆍ이상훈ㆍ이연아 ····························································································· S25

　2. Factors and Outcomes of Diagnostic Delay in Korean Patients with Spondyloarthritis

Seo MR, Ryu HJ, Choi HJ, Beak HJ ····················································································································· S26

　3. Phenotype Difference in Familial Ankylosing Spondylitis (AS) Compared to Sporadic AS

Hye Won Kim, Hye Rim Choi, Su Bin Lee, Won Ik Chang, Hyun Jun Chae, Jin Young Moon,

Jisue Kang, Sungim Lee, Eun Young Lee ··········································································································· S27

　4. The Reliability and Validity of a Korean Translation of the ASAS Health Index

in Korean Patients with Ankylosing Spondylitis

Jung-Ho Choi, Kyung-Eun Lee, Dong-Jin Park, Yong-Wook Park, Shin-Seok Lee,

Tae-Hwan Kim, Tae-Jong Kim ···························································································································· S28

Free Paper Session (2-2)：SLE -Pathogenesis (Convention Hall B, 지하 2층)

　1. Mucosal-associated Invariant T Cell Deficiency in Systemic Lupus Erythematosus

조영난ㆍ김문주ㆍ진혜미ㆍ정현주ㆍ김재이ㆍ이정원ㆍ이경은ㆍ박동진ㆍ김태종

이신석ㆍ기승정ㆍ유대현ㆍ박용욱 ·························································································································· S29

　2. Human Adipose Derived Mesenchymal Stem Cells Induce the Expansion of Regulatory B Cells

and Ameliorate Autoimmunity in a Murine Model of Systemic Lupus Erythematosus

곽승기ㆍ박민정ㆍ윤지희ㆍ조미라ㆍ박성환 ·········································································································· S30

　3. CD40 Activated Human CD27-CD38Int Pre-naive B Cells Modulate CD4+ T Cell Activation

via IL-10 Production

Ji-Hyun Sim, Hang-Rae Kim, Jisoo Lee ············································································································ S31

　4. Delta Neutrophil Index as a Useful Marker for the Differential Diagnosis Between Flare and Infection

in Febrile Patients with Systemic Lupus Erythematosus

하유정ㆍ표정윤ㆍ박진수ㆍ박용범ㆍ이수곤ㆍ이상원 ··························································································· S32

Free Paper Session (2-3)：Drug Therapies (Convention Hall B, 지하 2층)

　1. The Concomitant Use of Meloxicam and Methotrexate did not Increase the Risk

of Silent Kidney or Liver Damage in Patients with Rheumatoid Arthritis

박희진ㆍ박민찬ㆍ박용범ㆍ이수곤ㆍ이상원 ·········································································································· S33

xiii

　2. Blood B Cell Counts as Predictor of Early Clinical Response after Rituximab in Patients

with Rheumatoid Arthritis

You Jae Kim, Bon San Koo, Yong-Gil Kim, Chang-Keun Lee, Bin Yoo ····················································· S34

　3. Efficacy and Safety of Tacrolimus in Active Rheumatoid Arthritis Patients Shown Unsuccessful

Response Against Methotrexate: Non-Comparative, Single Arm, Multi-Center, Phase 4 Study

Won Seok Lee, Sang-Il Lee, Myung-Soo Lee, Sung-Il Kim, Shin-Seok Lee, Wan-Hee Yoo ··············· S35

　4. The Effect of Uric Acid Lowering Therapy (ULT) in Preventing Comorbidity of Gout

and Acute Gout Attack, A Retrospective Study

Kowoon Joo, Won Park, Seong-Ryul Kwon, Mie-Jin Lim, Kyong Hee Jung, Hoyeon Joo ························· S36

Free Paper Session (3-1)：Fibromyalgia and Miscellaneous (Conference 1, 지하 1층)

　1. Relationship Between Body Mass Index, Fat Mass and Muscle Mass with Musculoskeletal Pain

in Community Residents

Jong Jin Yoo, Seung Hun Lim, Nam Han Cho, Hyun Ah Kim ········································································· S37

　2. The Symptom Severity of Fibromyalgia is Associated with Socioeconomic Status, not with Obesity

in Korean Patients with Fibromyalgia

Dong-Jin Park, Shin-Seok Lee, Seong-Ho Kim, Seong-Su Nah, Ji Hyun Lee,

Seong-Kyu Kim, Yeon-Ah Lee, Seung-Jae Hong, Hyun-Sook Kim, Hye-Soon Lee,

Hyoun Ah Kim, Chung-Il Joung, Sang-Hyon Kim ···························································································· S38

　3. The Significance of Ectopic Germinal Center in Minor Salivary Gland of Patients with Sjögren’s Syndrome

Kyung-Eun Lee, Dong-Jin Park, Jeong-Won Lee, Ji Hyoun Kang, Lihui Wen,

Tae-Jong Kim, Yong-Wook Park, Shin-Seok Lee ··························································································· S39

　4. The Ratio and Clinical Characteristics of IgG4-related Retroperitoneal Fibrosis Patients

Among Idiopathic RPF Patients

구본산ㆍ윤다림ㆍ홍석찬ㆍ김유재ㆍ김용길ㆍ이창근ㆍ유 빈 ············································································· S40

Free Paper Session (3-2)：Chondrocytes and Osteoarthritis (Conference 1, 지하 1층)

　1. Fibronectin Fragment Induces Procatabolic Effects Through TLR-2 and not TLR-4 Signaling Pathway

in Human Articular Chondrocytes

Eun Jeong Cheon, Su Jin Park, Hyun Ah Kim ··································································································· S41

　2. Association Between Body Composition and Knee Pain and Radiographic Knee Osteoarthritis

in Community Residents in Korea

I. J. Kim, D. H. Kim, J. Y. Jung, Y. W. Song, H. A. Kim ················································································· S42

　3. MicroRNA-558 Regulates the Expression of Cyclooxygenase-2 and IL-1β–induced Catabolic Effects

in Human Articular Chondrocytes

Su Jin Park, Eun Jeong Cheon, Hyun Ah Kim ··································································································· S43

　4. Metabolically Abnormal but Normal Weight, Metabolically Healthy Obesity, and Knee Osteoarthritis:

A Cross-sectional Study in Korean Women

이성근ㆍ김성호 ························································································································································ S44

Free Paper Session (3-3)：Health Services Research (Conference 1, 지하 1층)

　1. 한국의 종합 병원 외래에서 항-종양괴사인자 α (anti-TNF α) 치료에 한 보험 여 기 을

충족하는 류마티스 염 환자의 비율: 다기 , 비 재 , 찰 연구

김 담ㆍ김동욱ㆍ김상현ㆍ김완욱ㆍ김윤성ㆍ김현아ㆍ박성환ㆍ박용범ㆍ박 원ㆍ서창희ㆍ송영욱

심승철ㆍ윤보영ㆍ이상헌ㆍ이혜순ㆍ최정윤ㆍ허진욱ㆍ유대현 ··········································································· S45

　2. Systemic Review: Agreement between Tuberculin Skin Test (TST) and Interferon-gamma Release Assay (IGRA)

Blood Test for Latent TB Screening Among Patients with Rheumatic Diseases

Junhee Pyo, Dam Kim, Soo-Kyung Cho, Sang-Cheol Bae, Yoon-Kyoung Sung ······································ S46

xiv

　3. Current Status of Ultrasound Use in Rheumatology in Korea

Taeyoung Kang, Richard J. Wakefield, Paul Emery ··························································································· S47

　4. Predictors of Indeterminate INF-γ Release Assay in Rheumatic Diseases

정현주ㆍ김태종ㆍ김형상ㆍ김재이ㆍ김문주ㆍ진혜미ㆍ조영난ㆍ이정원ㆍ이경은

박동진ㆍ이신석ㆍ기승정ㆍ박용욱 ·························································································································· S48

Free Paper Session (3-4)：RA-Clinical Aspects (Conference 1, 지하 1층)

　1. Inflammatory Burden Predicts Carotid Plaque Progression and Clinical Cardiovascular Disease

in Rheumatoid Arthritis: the Second Year KARRA Cohort Study

Churl Hyun Im, Sang Hoon Kwon, Jung Soo Eun, Na Ri Kim, Eon Jeong Nam, Young Mo Kang ·········· S49

　2. 류마티스 염 환자에서 고 압이 심 계 험도와 질병경과에 미치는 향

최찬범ㆍ이지영ㆍ성윤경ㆍ조수경ㆍ고은미ㆍ김성규ㆍ김태종ㆍ김태환ㆍ방소영ㆍ심승철ㆍ유대현

윤보영ㆍ이성원ㆍ이신석ㆍ이재준ㆍ이지수ㆍ이혜순ㆍ전재범ㆍ정영옥ㆍ정원태ㆍ차훈석ㆍ최정윤

홍승재ㆍ배상철ㆍKorean Observational Study Network for Arthritis (KORONA) 연구자 ······························· S50

　3. Longitudinal Radiographic Analysis of Rheumatoid Wrist: Minimum 7 Year Follow-up

이광현ㆍ최완선ㆍ이창훈 ········································································································································· S51

　4. Elevated Serum Resistin Levels in Rheumatoid Arthritis with Periodontitis

Byoong Yong Choi, In Ah Choi, Myeong Jae Yoon, Hye Jin Oh, Hye Won Kim, Sung Hae Chang,

Eun Young Lee, Eun Bong Lee, Yong Moo Lee, Yeong Wook Song ····························································· S52

2013년 5월 11일(토)

Symposium：한국인 류마티스관절염 (Convention Hall A, 지하 2층)

　1. 류마티스 염 임상연구센터 구성과 목표

배상철 ······································································································································································ S55

　2. 류마티스 염 다기 코호트 구축과 임상약물역학연구

배상철 ········································································································································································ S57

　3. 류마티스 염 진단 후에 한 측 지표 연구

이수곤ㆍ박용범ㆍ심승철ㆍ강영모 ·························································································································· S61

　4. 류마티스 염 치료근거 확립을 한 연구자주도 임상시험 고안 수행

송영욱ㆍ신기철 ························································································································································ S63

　5. 류마티스 염 약물치료의 경제성평가

이의경 ········································································································································································ S64

　6. 류마티스 염 임상진료지침 개발

박성환 ········································································································································································ S69

Special Lectures (귀국보고) (Convention Hall B, 지하 2층)

　1. A Phosphoinositide 3-kinase (PI3K)-δ, γ Inhibitor

in Models of Rheumatoid Arthritis

Hae-Rim Kim ·························································································································································· S75

　2. Lymph Node Stromal Cells and Lymphotoxin in Immune Tolerance

박경수 ········································································································································································ S76

　3. Health Status and Outcomes in RA: Cross-national Comparison Study between South Korea and US

Yoon-Kyoung Sung ················································································································································· S82

　4. PPM1A and Its Autoantibody in Ankylosing Spondylitis

김용길 ········································································································································································ S84

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Invited Lecture III (Convention Hall B, 지하 2층)

　1. Innate Immune Responses and Gut Homeostasis

Kiyoshi Takeda ························································································································································· S87

Free Paper Session (1-3)：RA-Pathogenesis (II) (Convention Hall A, 지하 2층)

　1. Smoking, The HLA-DRB1 Shared Epitope and ACPA Fine-specificity in Koreans with Rheumatoid

Arthritis: Evidence for more than One Pathogenic Pathway Linking Smoking to Disease

So-Young Bang, Benjamin A. Fisher, Muslima Chowdhury, Hye-Soon Lee, Jae-Hoon Kim,

Peter Charles, Patrick Venables, Sang-Cheol Bae ··························································································· S91

　2. DICAM Inhibits Angiogenesis Via Suppression of AKT and p38 MAP Kinase Signaling

Seung-Woo Han, Youn-Kwan Jung, Eun-Ju Lee, Hye-Ri Park, Gun-Woo Kim ······································· S92

　3. Interleukin-33 Acts as a Transcriptional Repressor and Extracellular Cytokine in Fibroblast-like

Synoviocytes in Patients with Rheumatoid Arthritis

이은주ㆍ소민욱ㆍ김용길ㆍ유 빈ㆍ이창근 ············································································································ S93

　4. Serum Dickkopf-1/R Spondin-1 Ratio is a Novel Biomarker for Wnt Signaling Status in Patients

with Rheumatoid Arthritis

Byoong Yong Choi, Hyon Joung Cho, Eun Ha Kang, Kichul Shin, Yeong Wook Song, Yun Jong Lee ····· S94

Free Paper Session (1-4)：TNF Inhibitor-related Issues (Convention Hall A, 지하 2층)

　1. Mortality in Patients with Rheumatoid Arthritis-associated Interstitial Lung Disease Treated

with an Anti-tumor Necrosis Factor Agent

구본산ㆍ김유재ㆍ소민욱ㆍ김용길ㆍ이창근ㆍ유 빈 ····························································································· S95

　2. Drug Survival Rates of Anti-Tumor Necrosis Factor Therapies in Patients with Rheumatoid Arthritis

and Ankylosing Spondylitis

Jeong-Won Lee, Dong-Jin Park, Kyung-Eun Lee, Ji Hyoun Kang, Lihui Wen, Tae-Jong Kim,

Yong-Wook Park, Shin-Seok Lee ······················································································································· S96

　3. 강직성 척추염에서 종양괴사인자 차단제의 도량학 효과에 한 측 인자

남언정ㆍ권상훈ㆍ은종수ㆍ김나리ㆍ임철현ㆍ강영모 ··························································································· S97

　4. TNF 길항제가 응이 되는 류마티스 염 환자들의 임상양상

손경민ㆍ김범준ㆍ문소영ㆍ서영일ㆍ정영옥ㆍ김인제ㆍ이성연ㆍ김현아 ···························································· S98

Free Paper Session (2-4)：SLE-Clinical Aspects (Convention Hall B, 지하 2층)

　1. Hydroxychloroquine 망막병증의 선별검사 결과

김상진ㆍ황지원ㆍ이민규ㆍ이재준ㆍ차훈석ㆍ고은미 ··························································································· S99

　2. Comparison of Mycophenolate Mofetil and Intravenous Cyclophosphamide as Induction Therapy

in Korean Patients with Lupus Nephritis

Dong-Jin Park, Ji-Hyoun Kang, Kyung-Eun Lee, Jeong-Won Lee, Lihui Wen, Tae-Jong Kim,

Yong-Wook Park, Ji Shin Lee, Yoo Duk Choi, Shin-Seok Lee ······································································ S100

　3. Persistent Dyslipidemia is a Risk Factor of Progression to Chronic Kidney Disease

in Patients with Lupus Nephritis

Dong-Jin Park, Ji-Hyoun Kang, Kyung-Eun Lee, Jeong-Won Lee, Lihui Wen, Tae-Jong Kim,

Yong-Wook Park, Ji Shin Lee, Yoo Duk Choi, Shin-Seok Lee ······································································ S101

　4. The Assessment of Psychological Stress Using Saliva in SLE

Ju-Yang Jung, Chang-Bum Bae, Jin-Young Nam, Hyoun-Ah Kim, Chang-Hee Suh ····························· S102

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Free Paper Session (2-5)：RA-Pathogenesis (III) (Convention Hall B, 지하 2층)

　1. Foxp3-Expressing Regulatory B Cells Inhibit Autoimmune Arthritis in a Mouse Model

Mi-Kyung Park, Young Ok Jung, Yu-Jung Heo, Eun-Kyung Kim, Hye-Jwa Oh,

Young-Mee Moon, Sung-Hwan Park, Ho-Youn Kim, Mi-La Cho, Jun-Ki Min ········································ S103

　2. Treatment of Collagen-induced Arthritis Using Immune Modulatory Properties

of Human Mesenchymal Stem Cells

박규형ㆍ문진희ㆍ강미일ㆍ이상원ㆍ이수곤ㆍ박용범 ··························································································· S104

　3. Regulation of Apoptosis and Inflammatory Responses by IGFBP-3 in Fibroblast-like Synoviocytes

and Experimental Animal Models of Rheumatoid Arthritis

Hwa-Suk Lee, Seong Ji Woo, Sun-O Ka, Hye Song Lim, Hyun-Ok Kim,

Byung-Hyun Park, Sang-Il Lee ··························································································································· S105

　4. CD70 Expressing CD4 T Cells Produce IFN-γ and IL-17 in Rheumatoid Arthritis

박진균ㆍ한광훈ㆍ박지아ㆍ우윤정ㆍ김소영ㆍ이은영ㆍ이은봉ㆍ송영욱 ···························································· S106

Free Paper Session (3-5)：Myositis and AOSD (Conference 1, 지하 1층)

　1. The Potential Role of Mast Cells in the C-Protein Induced Myositis Model

신기철ㆍ김은영ㆍ최지용ㆍ장성혜ㆍ송영욱 ·········································································································· S107

　2. The Effect of CXCL10 Blockade in C Protein-induced Myositis

Jinhyun Kim, Jiyong Choi, Sung-Hye Park, Seung Hee Yang, Ji Ah Park, Kichul Shin,

Eun Young Lee, Eun Bong Lee, Hiroshi Kawachi, Hitoshi Kohsaka, Yeong Wook Song ···························· S108

　3. Delta Neutrophil Index as an Early Marker for Differential Diagnosis of Adult-onset

Still’s Disease and Sepsis

박희진ㆍ하유정ㆍ표정윤ㆍ박용범ㆍ이수곤ㆍ이상원 ··························································································· S109

　4. Biomarkers as Reflecting Disease Activity in Korean Patients with Adult Onset Still’s Disease

Jin-Ju Kim, Jae-Kong Kim, Dae-Hyun Yoo ····································································································· S110

Free Paper Session (3-6)：Epidemiology (Conference 1, 지하 1층)

　1. Prevalence of and Risk Factors for Spine OA and Its Association with Low Back Pain

Among Community Residents in Korea

Sung Yeon Lee, Young Ok Jung, Hyun Ah Kim, Seung Hun Lim, Nam Han Cho ······································· S111

　2. Prevalence and Incidence of Osteonecrosis in Patients with Systemic Lupus Erythematosus

Young Bin Joo, Yoon-Kyoung Sung, Jee-Seon Shim, Jae-Hoon Kim,

Hye-Soon Lee, Sang-Cheol Bae ························································································································ S112

　3. Prevalence and Incidence of Systemic Lupus Erythematosus in South Korea

Jee-Seon Shim, Yoon-Kyoung Sung, Jae-Hoon Kim, Hye-Soon Lee, Sang-Cheol Bae ······················· S113

활막염연구회

Special Lectures I (Conference 3, 지하 1층)

　1. Intracellular Heparin Alleviates T Cell-mediated Inflammatory Arthritis by Inhibiting

RhoA-dependent Transcellular Diapedesis

Young Mo Kang ······················································································································································· S117

　2. Autophagy: An Innate Immune Effector Against Mycobacteria

Eun-Kyeong Jo ························································································································································ S118

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　3. Mycobacterium Tuberculosis Heparin-binding Hemagglutinin and HspX, A Novel TLR4 Agonist,

Induces Dendritic Cells-based Immunotherapy Via Drives Th1 Immune Response

In Duk Jung, Hyun Kyu Kang, Yeong-Min Park ································································································ S119

Oral Presentation I (Conference 3, 지하 1층)

　1. Dysfunction of Natural Killer T Cells in Patients with Active Mycobacterium tuberculosis Infection

Young-Nan Cho, Seung-Jung Kee, Yong-Soo Kwon, Sung-Ji Lee, Hye-Mi Jin, Mun-Ju Kim,

Jae-Yee Kim, Hyun-Ju Jung, Tae-Jong Kim, Shin-Seok Lee, Yong-Wook Park ····································· S123

　2. 류마티스 염 환자의 액유래 간엽 기세포의 질환시기에 따른 분화 면역억제능의 차이

김현옥ㆍ천윤홍ㆍ하영술ㆍ임혜송ㆍ이원재ㆍ이성림ㆍ이상일 ··········································································· S124

어떻게 실험을 시작할 것인가? (활막염 연구회 홈페이지 활용 Tips) (Conference 3, 지하 1층)

　1. 어떻게 실험을 시작할 것인가? (활막염 연구회 홈페이지 활용 Tips)

이명수 ········································································································································································S127

Special Lectures II (Conference 3, 지하 1층)

　1. Techniques in Human T Cell Study: Application for Rheumatology

신의철 ········································································································································································ S131

　2. Genetic Predispositions to Rheumatoid Arthritis and Lupus

Taehyeung Kim, Kwangwoo Kim, Tae-Un Han, Changsoo Paul Kang, Changwon Kang ··························· S132

Oral Presentation II (Conference 3, 지하 1층)

　1. Leukocyte-Specific Protein 1 (LSP-1) Is A Negative Regulator of T Cell Migration

Seong-Hye Hwang, Nam-Hoon Kim, Seung-Ah Yoo, Chul-Soo Cho, Wan-Uk Kim ······························· S135

　2. PH-responsive Nanoparticles Carrying Methotrexate for Treatment of Inflammatory Arthritis

Shijin Sung, Mahmudul Md Alam, Jin Hee Kang, Hasan Al Faruque, Keum Hee Sa,

Jae Hyung Park, Young Mo Kang ························································································································· S136

　3. Oleanolic Acid Acetate Inhibits Osteoclast Differentiation by Downregulating

PLCγ2-Ca2+-NFATc1 signaling, and Suppresses bone loss in mice

Chang Hoon Lee, Ju-Young Kim, Jaemin Oh, Myeung Su Lee ····································································· S137

류마티즘골대사연구회

제1부(Convention Hall A, 지하 2층)

　1. Runx2 Stability and Transcriptional Activity is Regulated by Pin1

Hyun-Mo Ryoo ························································································································································ S141

제2부(Convention Hall A, 지하 2층)

　1. Oxidative Stress & Osteoporosis

민준기 ········································································································································································ S145

　2. Regulatory T Cells in HLA B27 Transgenic Rats

권성렬 ········································································································································································ S148

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통풍연구회

제1부 통풍(Convention Hall B, 지하 2층)

　1. 환자에게 배우는 통풍이야기

김현옥 ········································································································································································ S151

　2. 한국인에서 Sugar-sweetened Soft Drink와 요산의 계

김성규 ········································································································································································ S157

　3. 2012 ACR Guidelines for Management of Gout

송정수 ········································································································································································ S159

　4. 통풍의 진료지침개발을 한 제안

김현아 ········································································································································································ S165

제2부 가성통풍(Convention Hall B, 지하 2층)

　1. 부갑상선기능항진증에 의한 가성통풍; 증례

전재범 ········································································································································································ S169

　2. CPPD 질환의 용어, 진단 치료에 한 유럽류마티스학회의 권고사항

전찬홍 ········································································································································································ S170

척추관절염연구회

제1부(Conference 1, 지하 1층)

　1. Is AS a Genetic Disease?

Seung Cheol Shim ·················································································································································· S179

　2. 건선 염 정말 드문가? -역학, 진단, 치료

백한주 ········································································································································································ S180

제2부(Conference 1, 지하 1층)

　1. Recent Update in MRI Studies for Axial Spondyloarthritis

Kichul Shin ······························································································································································· S183

　2. 강직성 척추염의 치료 리

김태종 ········································································································································································ S184

xix

Poster Presentation (Convention Hall C)

　1. Monosodium Urate Crystal Enhanced Osteoclastogenesis Through TRAF-6 Signaling Pathway

in RAW 264.7 Macrophage Cells

박기연ㆍ김성규ㆍ이화정ㆍ김주현ㆍ최정윤 ·········································································································· S191

　2. Clinical Significance of Caspase-1 Level in Synovial Fluid from Patients with Gout and Other Arthritides

손창남ㆍ방소영ㆍ김지해ㆍ최찬범ㆍ김태환ㆍ전재범 ··························································································· S192

　3. MicroRNA-155 as a Proinflammatory Regulator in Acute Gouty Arthritis

Hye-Mi Jin, Jung-Ho Choi, Moon-Ju Kim, Young-Nan Cho, Kwang-Il Nam, Seung-Jung Kee,

Jang Bae Moon, Dong-Jin Park, Yong-Wook Park, Shin-Seok Lee, Tae-Jong Kim ································ S193

　4. Quality of Life in Chronic Gouty Arthritis Patients; Comparison Between Patients with or without Tophi

김지혜ㆍ박지원ㆍ구본승ㆍ이태진ㆍ송영욱ㆍ신기철 ··························································································· S194

　5. Elevated Serum Homocysteine Levels in Gouty Patients were Related not with

Serum Uric Acid Levels but with Decreased Renal Function

Jin Su Kim, Eun Hye Park, SangTae Choi, Jung-Soo Song ··········································································· S195

　6. Changes in Bone Mineral Density in Patients with Recent-onset Rheumatoid Arthritis

You Jae Kim, Bon San Koo, Yong-Gil Kim, Chang-Keun Lee, Bin Yoo ····················································· S196

　7. The Prevalence of and Risk Factors for Osteoporosis in Patients with Rheumatoid Arthritis in South Korea

Joo-Hyun Lee, Yoon-Kyoung Sung, Jeeseon Shim, Chan-Bum Choi, Soo-Kyung Cho,

So-Young Bang, Jung-Yoon Choe, Seung-Jae Hong, Jae-Bum Jun, Tae-Hwan Kim,

Jisoo Lee, Hye-Soon Lee, Dae-Hyun Yoo, Bo Young Yoon, Sang-Cheol Bae ·········································· S197

　8. Are Glucocorticoid-Induced Osteoporosis Recommendations Sufficient to Determine Anti-Osteoporotic

Treatment for Patients with Rheumatoid Arthritis?

Joo-Hyun Lee, Soo-Kyung Cho, Minkyung Han, Dam Kim, Sang-Cheol Bae, Yoon-Kyoung Sung ······ S198

　9. 생물학 제재와 NSAIDs를 사용하는 강직성 척추염 환자에서 골 도의 변화에 한 비교 연구

이상엽ㆍ임상우ㆍ이성원ㆍ정원태 ·························································································································· S199

10. Coenzyme Q10 Ameliorates Pain and Cartilage Degradation in a Rat Model of Osteoarthritis

by Regulating Nitric Oxide and Inflammatory Cytokines

이주하ㆍ홍연식ㆍ정정희ㆍ양은지ㆍ전주연ㆍ박미경ㆍ정영옥ㆍ민준기ㆍ조미라ㆍ박성환 ····························· S200

11. Clinical Courses and Predictors of Outcomes in Patients with Monoarthritis:

a Retrospective Study of 171 Cases

Hyemin Jeong, In Young Kim, Eun-Jung Park, Jiwon Hwang, Hyungjin Kim,

Joong Kyong Ahn, Jaejoon Lee, Eun-Mi Koh, Hoon-Suk Cha ······································································ S201

12. HMGB1 Regulates Hypoxia-inducible Factor 1α Expression and Function

in Synovial Fibroblasts from Patients with Rheumatoid Arthritis

박소연ㆍ김혜영ㆍ홍기환ㆍ김치대 ·························································································································· S202

13. Reciprocal Activation of CD4+T Cells and Synovial Fibroblasts by Stromal Cell-derived Factor (SDF)-1

Promotes RANKL Expression and Osteoclastogenesis in Rheumatoid Arthritis

김해림ㆍ김경운ㆍ김보미ㆍ조미라ㆍ이상헌 ·········································································································· S203

14. Caspase-5 Inhibitor 처치에 따른 류마티스 염 활막세포에서의 활막세포 증식의

억제 염증매개인자 감소 효과

권용진ㆍ김태연ㆍ이상원ㆍ송정식ㆍ박용범ㆍ이수곤ㆍ박민찬 ··········································································· S204

15. Rebamipide Suppresses Collagen-induced Arthritis Through Reciprocal Regulation of Th17/Treg

Differentiation and Heme Oxygenase-1 Induction

Su-Jin Moon, Jin-Sil Park, Mi-La Cho, Jun-Ki Min ······················································································ S205

16. Kaempferol Inhibitis IL-1β-induced Proliferation and Production of MMPs, COX-2 and PGE2

by Rheumatoid Synovial Fibroblasts

Pil-Hun Song, Yun-Jung Choi, Ha-Yong Yoon, Eun-Gyeong Lee,

Myung-Soon Sung, Won Seok Lee, Wan-Hee Yoo ························································································· S206

17. Serum IL-34 Level is Associated with Radiographic Progression in Early Rheumatoid Arthritis

장성혜ㆍ최병용ㆍ조현정ㆍ강은하ㆍ이윤종 ·········································································································· S207

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18. Increased Level of IL-34 in Serum and Synovial Fluid is Associated with Rheumatoid Factor

and Anti-cyclic Citrullinated Peptide Antibody Titers in Patients with Rheumatoid Arthritis

문수진ㆍ홍연식ㆍ주지현ㆍ박성환ㆍ민준기 ·········································································································· S208

19. Plasma Leucine-rich alpha-2 Glycoprotein is a Useful Disease Activity Biomarker in Rheumatoid Arthritis

하유정ㆍ최상태ㆍ송정수ㆍ강은진ㆍ이상원ㆍ박용범ㆍ이수곤 ··········································································· S209

20. Relation of Rheumatoid Factor and Anti-cyclic Citrullinated Peptide Antibody

with Disease Activity in Rheumatoid Arthritis: Cross-sectional Study

Seong-Kyu Kim, Jisuk Bae, Hwajeong Lee, Jung-Yoon Choe ······································································· S210

21. Effects of Early Diagnosis on Disease Activity and Functional Disability in Rheumatoid Arthritis:

Cross-sectional Study of the KORONA Cohort Database

Dam Kim, Chan-Bum Choi, Jiyoung Lee, Yoon-Kyoung Sung, Soo-Kyung Cho, Bo Young Yoon,

Dae-Hyun Yoo, Eunmi Koh, Hoon-Suk Cha, Hye-Soon Lee, Jae-Bum Jun, Jaejoon Lee, Jinseok Kim,

Jisoo Lee, Jung-Yoon Choe, Sang-Heon Lee, Seong-Kyu Kim, Seung-Cheol Shim, Seung-Jae Hong,

Shin-Seok Lee, So-Young Bang, Sung Won Lee, Tae-Hwan Kim, Tae-Jong Kim, Won Tae Chung,

Young Ok Jung, Sang-Cheol Bae ························································································································ S211

22. Musculoskeletal Ultrasonography of Distal Lower Extremities in Rheumatoid Arthritis;

A Pilot Study of 50 Patients

구본승ㆍ이정찬ㆍ신기철 ········································································································································· S212

23. 류마티스 염 환자에서 TNF길항제 투여 후 결핵발생률 연구

서기현 ········································································································································································ S213

24. Cancers in RA Patients

Hwajeong Lee, Jisuk Bae, Seong-Kyu Kim, Jung-Yoon Choe ······································································· S214

25. Vitamin D Deficiency Can be a Risk Factor for the Presence of Rheumatoid Arthritis Among

Patients with Inflammatory Arthritis

Seung-Geun Lee, Geun-Tae Kim, Seong-Hu Park, Joung-Wook Lee,

Jun-Hee Lee, Seung-Hoon Baek, Young-Eun Park ······················································································· S215

26. The Association of Serum Vitamin D and 10-year Cardiovascular Risk in Patients with Rheumatoid Arthritis

정승민ㆍ이재호ㆍ서영선ㆍ고정희ㆍ이주하ㆍ곽승기ㆍ박경수ㆍ박성환 ···························································· S216

27. Association of Body Mass Index with Disease Activity in Patients with Rheumatoid Arthritis:

Focus on Disease Activity Indices and Composites

Jung-Yoon Choe, Hwajeong Lee, Seong-Kyu Kim ·························································································· S217

28. Association Between Vitamin D Deficiency and Obesity in Patients with Rheumatoid Arthritis

Jae Ho Lee, Jung Hee Koh, Young Sun Suh, Jennifer Lee, Seung-Min Jung,

Seung-Ki Kwok, Kyung-Su Park, Sung-Hwan Park ························································································ S218

29. Prognostic Impact of Functional Outcome in Patients with Rheumatoid Arthritis - Prospective Cohort Study

Na Ri Kim, Jung Soo Eun, Sang Hoon Kwon, Churl Hyun Im, Eon Jeong Nam, Young Mo Kang ·········· S219

30. Impact of Etanercept-Methotrexate Therapy on Patient-Reported Outcomes in Moderately Active

Rheumatoid Arthritis: Korean Results from the Induction Period of Preserve Trial

Min-Chan Park, Sang-Heon Lee, Hyun Ah Kim, In-Je Kim, Hyun-Jeong Yoo ········································· S220

31. Immunogenicity of Anti-tumor Necrosis Factor Therapy in Korean Patients

정승민ㆍ김현숙ㆍ김해림ㆍ곽승기ㆍ박경수ㆍ박성환ㆍ김호연ㆍ주지현 ···························································· S221

32. Growth Arrest-Specific 6 (GAS6) Gene Polymorphisms are Associated with Clinical Manifestations

of Systemic Lupus Erythematosus in Koreans

Ja Young Jeon, Bong-Sik Kim, Chang Hee Suh ······························································································· S222

33. Autoantibodies to C-reactive Protein may not Predict the Progression of Incomplete Lupus

to Systemic Lupus Erythematosus

Ju-Yang Jung, Bo-Ram Koh, Chang-Bum Bae, Hyoun-Ah Kim, Ja-Young Jeon, Chang-Hee Suh ···· S223

34. Anti-ribosomal P Antibody may be Associated with Protective Role in Patients with Lupus Nephritis

Dong-Jin Park, Ji-Hyoun Kang, Kyung-Eun Lee, Jeong-Won Lee, Lihui Wen,

Tae-Jong Kim, Yong-Wook Park, Ji Shin Lee, Yoo Duk Choi, Shin-Seok Lee ········································· S224

xxi

35. 신홍반루푸스 환자에서 경동맥 경직도와 경동맥 동맥경화와의 련성

이홍직ㆍ이지현 ························································································································································ S225

36. Association Between Arterial Stiffness and Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus

이홍직ㆍ이지현 ························································································································································ S226

37. Smoking Increases Systemic Lupus Erythematosus Susceptibility

Ji-Young Choi, So-Young Bang, Hye-Soon Lee, Sang-Cheol Bae ····························································· S227

38. Pregnancy Outcomes in Korean Patients with Systemic Lupus Erythematosus and Antiphospholipid

Antibodies: A Single Center Experience

Jung Hee Koh, Hyun Sun Ko, Jae Ho Lee, Jennifer Lee, Seung Min Jung,

Young Sun Suh, Seung-Ki Kwok, Kyung-Su Park, Sung-Hwan Park ························································· S228

39. Increased Expression of Interleukin 33 in Sera and Salivary Gland from Patients with Sjogren Syndrome

정승민ㆍ이재호ㆍ서영선ㆍ고정희ㆍ이주하ㆍ박경수ㆍ박성환ㆍ곽승기 ···························································· S229

40. Impact of Fractalkine (CX3CL1) in Primary Sjogren’s Syndrome: Its Expression in Labial Salivary Gland

Jae Ho Lee, Jung Hee Koh, Young Sun Suh, Jennifer Lee, Seung-Min Jung,

Kyung-Su Park, Sung-Hwan Park, Seung-Ki Kwok ························································································ S230

41. Microvascular Findings in Patients with Raynaud’s Disease - Assessed by Nailfold Capillaroscopy

and Flow Mediated Dilatation

이홍직ㆍ이지현 ························································································································································ S231

42. Cross-cultural Adaptation and Validation of a Korean Version of the Behcet’s Disease

Current Activity form 2006

Hyo Jin Choi, Suk Ho Kang, Mi Ryung Seo, Hee Jung Ryu, Han Joo Baek ················································· S232

43. Pilot Trial of Tocilizumab for Refractory Patients with Adult Onset Still’s Disease

Jin-Ju Kim, Tae-Hwan Kim, Dae-Hyn Yoo ······································································································ S233

44. 강직성 척추염의 활액막 세포에서의 TLR2와 TLR 4의 발

이상엽ㆍ배재호ㆍ임상우ㆍ이성원ㆍ정원태 ·········································································································· S234

45. The Impact of Thyroid Autoimmunity on Arterial Stiffness in Postmenopausal Female Patients with Fibromyalgia

이홍직ㆍ이지현 ························································································································································ S235

46. Smart App for Diagnosing and Evaluating of Activity of Rheumatic Diseases

Choong Won Lee, Sung Won Lee, Hyun Sung Lee ··························································································· S236

47. 통풍환자에서 생긴 다발성 무 성 골두 괴사

하명수ㆍ오수진ㆍ김송이ㆍ이창훈ㆍ이명수 ·········································································································· S237

48. 귀안의 염증성 용종으로 처음 확인되었던 통풍성 결 의 1

윤명재ㆍ오혜진ㆍ구본승ㆍ이준호ㆍ이은봉 ·········································································································· S238

49. 일차성 부갑상선 기능항진증으로 인한 칼슘피로인산 결정침착 질환 1

손창남ㆍ김 담ㆍ주경빈ㆍ이승훈ㆍ이지영ㆍ김동선ㆍ송영수ㆍ태 경ㆍ유태석ㆍ전재범 ································· S239

50. A Case of Atypical Femur Fracture in a Patient with RA with Long-term Bisphosphonate Therapy

Chang-Nam Son, Sodam Jung, Dam Kim, Ji-Young Choi, Seunghun Lee,

Yi-Suk Kim, Yoon-Kyoung Sung ························································································································· S240

51. 셀 콕시 사용 후 발생한 Sweet 신드롬의 증례1

정소담ㆍ이지영ㆍ김 담ㆍ손창남ㆍ고주연ㆍ박찬금ㆍ유대현 ············································································· S241

52. 류마티스 염 환자에서 종양괴사인자 억제제 사용 발생한 미만성 폐포 출 1

김혜진ㆍ조홍성ㆍ김윤성ㆍ김현숙 ·························································································································· S242

53. 류마티스 염 환자에서 발생한 치아돌기 비외상골

배승현ㆍ김용길ㆍ신명진ㆍ전상용ㆍ윤다림ㆍ홍석찬ㆍ김유재ㆍ구본산ㆍ이창근ㆍ유 빈 ······························· S243

54. A Case of Renal AA Amyloidosis and Chronic Kidney Disease in Patient with Rheumatoid Arthritis

with a Good Response to Etanercept

Hyun Woo Kim, Jung Won Noh, Jinseok Kim ····································································································· S244

55. 류마티스 염에서 발병한 성 신부 다발성 골수종 증례

황선혁ㆍ배창범ㆍ정주양ㆍ김현아ㆍ정성현ㆍ서창희 ··························································································· S245

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56. A Case of Renal Lupus Vasculitis with Pauci-immune Glomerulonephritis

in Patient with Systemic Lupus Erythematosus

Eun-Jung Park, Sung Hyun Kim, Jinseok Kim ·································································································· S246

57. 신홍반루푸스 환자에서 발생한 피막성 경화복막염 1

배상철ㆍ이주현ㆍ김유선ㆍ나종천ㆍ윤보영 ·········································································································· S247

58. Acute Inflammatory Demyelinating Polyradiculoneuropathy in Patient with Systemic Lupus Erythematosus

Jeong-Won Lee, Dong-Jin Park, Kyung-Eun Lee, Ji Hyoun Kang, Lihui Wen,

Tae-Jong Kim, Yong-Wook Park, Shin-Seok Lee ··························································································· S248

59. 루푸스 환자에서 스테로이드 충격 요법 후 발생한 폐출 에서 Rituximab을 이용한 치료 1

임상우ㆍ이상엽ㆍ이성원ㆍ정원태 ·························································································································· S249

60. 신홍반루푸스 환자에서 Cyclophosphamide Pulse 치료 후 발생한 스트 스 유발성 심근증 1

이유호ㆍ송 란ㆍ이상훈ㆍ이연아ㆍ홍승재ㆍ양형인 ····························································································· S250

61. 쇼그 증후군 환자에서 흉선과 폐를 침범한 MALT림 종 1

오혜진ㆍ윤명재ㆍ구본승ㆍ이상진ㆍ김경록ㆍ전윤경ㆍ송영욱 ··········································································· S251

62. Primary Sjögren's Syndrome in Identical Twin

Yu-Ji Kim, Yun-Jung Choi, Ha-Yong Yoon, Won Seok Lee, Wan-Hee Yoo ············································· S252

63. Pulmonary Nodular Amyloidosis in Patients with Sjögren's Syndrome

In-Suk Min, Yun-jung Choi, Ha-Yong Yoon, Won Seok Lee, Wan-Hee Yoo ··········································· S253

64. 증 다발성 근염 환자에서 동반된 심장 사르코이드증 1

권상훈ㆍ은정수ㆍ김나리ㆍ임철현ㆍ남언정ㆍ강영모 ··························································································· S254

65. Asymmetrical Involvement of Lower Leg Muscle, Confused as a Focal Myositis by Infection,

in a Dermatomyositis Patient Under Treatment

황순우ㆍ이지영ㆍ정소담ㆍ김 담ㆍ손창남ㆍ유대현 ····························································································· S255

66. Dermatomyositis Associated with Gallbladder Cancer

Jin Su Park, Jung Yoon Pyo, Moon Jae Chung, Jung Sik Song, Yong-Beom Park,

Soo-Kon Lee, Sang-Won Lee ····························································································································· S256

67. A Case of Immunoglobulin G4-rich Synovitis in a Patient with Ankylosing Spondylitis

구본승ㆍ윤명재ㆍ오혜진ㆍ윤필환ㆍ김지은ㆍ신기철 ··························································································· S257

68. 강직성 척추염과 베체트병이 동반된 환자에서 Etanercept에 의해 성공 으로 치료된 1

임균섭ㆍ김진우ㆍ김성중ㆍ소중해ㆍ김동현ㆍ김형호ㆍ김현숙ㆍ김윤성 ···························································· S258

69. 신성 경화증 환자에서 발생한 동기능부 증후군 1

김동현ㆍ김성중ㆍ소중해ㆍ김형호ㆍ김현숙ㆍ김윤성 ··························································································· S259

70. 헤노흐-쉔라인 자반증과 동반된 거 세포바이러스 장염 1

은정수ㆍ권상훈ㆍ김나리ㆍ임철현ㆍ남언정ㆍ강영모 ··························································································· S260

71. Enterocolic Phlebitis: One Cause of Localized Vasculitis of the Gastrointestinal Tract

MR Seo, TE Kim, HJ Ryu, HJ Baek, HJ Choi ······································································································ S261

72. A Case of Multicentric Reticulohistiocytosis Responsive to Leflunomide

Young Bin Joo, Ki-seok Jang, Dae-Hyun Yoo ································································································· S262

73. 난치성 성인형 스틸병 환자에서 Abatacept로 치료를 시도한 환자 5

윤명재ㆍ오혜진ㆍ구본승ㆍ주상현ㆍ김경록ㆍ이은영 ··························································································· S263

74. A Case of Primary Biliary Cirrhosis in Overlap Syndrome of Systemic Sclerosis and Rheumatoid Arthritis

Kyoung Hwa Lee, Mi Ryoung Seo, Han Joo Baek, Hyo Jin Choi ···································································· S264

75. A Case of Behçet's Disease with Esophagopharyngeal Ulcers

Jin-Won Jang, Yun-Jung Choi, Ha-Yong Yoon, Won Seok Lee, Wan-Hee Yoo ······································· S265

76. 흉선종과 동반하여 나타난 자가면역 병증 1

정신옥ㆍ김현숙 ························································································································································ S266

77. Dysphagia Caused by Ossification of the Cervical Anterior Longitudinal Ligament

곽윤미ㆍ김현숙 ························································································································································ S267

(2010. 1. 1∼2010. 12. 31)

The 33th Korean College of Rheumatology Annual Scientific Meeting and the 7th International Symposium

International Symposium

J o u r n a l o f R h e u m a t i c D i s e a s e sV o l . 2 0 , S u p p l . 1 , M a y , 2 0 1 3

S3

The Anti-angiogenic, Anti-tumor and Anti-osteoclast Functions of Cartilage

Department of Orthopaedic Surgery, Washington University, USA

Linda J. Sandell

Cartilage tissue is avascular and resistant to tumor invasion, but the basis for these properties is still unclear. Here we report

that the NH2-propeptide of type IIB procollagen (PIIBNP), a product of collagen biosynthesis, is capable of inhibiting angiogenesis

both in vitro and in vivo. PIIBNP inhibits tube formation in human umbilical vein cells (HUVEC), suppresses endogenous endothe-

lial cell outgrowth in rat aortic ring angiogenesis bioassay and is anti-angiogenic in the mouse cornea angiogenesis assay. PIIBNP

also shrinks chondrosarcoma tumor in nude mice. Both cartilage and conditioned medium of chondrocytes from new born mice

inhibits microvessel outgrowth in mouse aortic ring assays, and PIIBNP is detected from cartilage and the conditioned medium.

PIIBNP induces Src kinase activation, disrupts VE-cadherin localization at HUVEC cell contact and promote β-catenin degrada-

tion, suggesting that PIIBNP inhibits angiogenesis through negative regulation of Wnt signaling. As αVβ3 and αVβ5 integrins

are expressed primarily on endothelial cells, cancer cells and osteoclasts, but not on normal chondrocytes and PIIBNP binds

to cell surface integrin αVβ3 and αVβ5, we propose that natural occurring PIIBNP protects cartilage by targeting endothelial

cells during chondrogenesis, thus inhibiting angiogenesis and rendering the tissue avascular.


S4

Hypoxia-inducible Factor-2α Regulation of Osteoarthritis and Rheumatoid Arthritis

School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Korea

Jang-Soo Chun

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by articular cartilage destruction. Biophysical and bio-

chemical factors, including mechanical stress and pro-inflammatory cytokines, respectively, are responsible for the activation of

catabolic pathways and initiation of OA cartilage destruction. Activation of certain biochemical pathways in chondrocytes—unique

resident cells that synthesize cartilage-specific extracellular matrix (ECM) components as well as various catabolic and anabolic

factors—eventually leads to cartilage destruction. Among the articular chondrocyte biochemical pathways important in this context

are those leading to the production of matrix metalloproteinases (MMPs) and ADAMTS (a disintegrin and metalloproteinases

with thrombospondin motifs), which are involved in the degradation of the ECM. However, the molecular pathogenic mechanisms

of OA are not understood in sufficient detail to allow the development of effective therapeutic targets for OA treatment. This

talk will introduce our recent findings of novel catabolic and anabolic factors regulating osteoarthritic (OA) cartilage destruction.


S5

DAMP Signaling in Osteoarthritis

Hallym University

Hyun Ah Kim

Articular cartilage consists of an abundance of extracelullar matrix (ECM), the degradation of which is a central event leading

to joint destruction in many arthritic conditions including rheumatoid arthritis (RA), osteoarthritis (OA) and septic arthritis.

Chondrocytes respond to a variety of stimuli such as proinflammatory cytokines and mechanical loading by elaborating degradative

enzymes and catabolic mediators.

The innate immune system comprises the cells and mechanisms that defend the host from infection by other organisms in a

non-specific manner. Unlike the adaptive immune system, it does not confer long-lasting or protective immunity to the host.

Besides host-defensive function such as recruiting of immune cells to sites of infection, and activation of the complement cascade

to identify bacteria, activate cells and to promote clearance of dead cells or antibody complexes, innate immune system identifies

and removes materials released during tissue or organ damage as well as foreign substances present in the blood and lymph.

Damage-associated molecular patterns (DAMPs) result from tissue injury, as a result of secretion, release and/or exposure on

the outer leaflet of the plasma membrane of intracellular molecules or from extracellular sources, such as the extracellular matrix

(e.g. hyaluronan and heparan sulfate). DAMPs modulate the immune system through innate system. DAMPS have the capacity

to affect the function of antigen-presenting cells as well as other cell types, such as eosinophils, mast cells and neutrophils.

The catabolic response induced with cartilage matrix degradation product is potentially important in the mediation of cartilage

degradation in arthritic disease, with the generation of matrix degradation product forming a viscious cycle of perpetuating cartilage

destruction by working as DAMPs. We previously reported that human articular cartilage express Toll-like receptor (TLR)s and

responds to TLR ligands by elaboration of catabolic mediators. In this symposium, we review previous studies implicating the

pathogenetic role of innate immune system and DAMP in OA cartilage degradation including our results obtained from FN-f,

an ECM glycoprotein degradation product found in OA synovial fluid

(2010. 1. 1∼2010. 12. 31)


Invited Lecture I


S9

Systemic Lupus - Cells, Signals, and Cytokines

Section of Rheumatology, Temple University School of Medicine and Temple Autoimmunity Center

Philip Cohen

Specific autoantibody production and hypergammaglobulinemia are well-defined features of systemic lupus erythematosus (SLE).

B cells from SLE patients have distinct phenotypic abnormalities, particularly in active disease, and secrete excessive amounts

of antibody. SLE T cells, in contrast, are present in reduced numbers and have been reported to produce increased amounts

of IL-6, IL-17, IL-21, and other cytokines. A role for defective T regulatory cells in SLE is under active investigation. It is

now also well established that increased production of type I interferons and of the products of interferon-inducible genes are

reproducibly found in active disease. Exogenous stimuli, possibly acting through Toll like receptors, trigger dendritic cell (DC)

production of interferons; and DCs, principally of the plasmacytoid variety, may drive T helper cells to assist in the production

of autoantibodies to nuclear proteins and nucleic acids.

The mechanisms controlling interferon production are complex and are undergoing intensive investigation. The recently dis-

covered RIG-I pathway is of particular interest, especially with respect to the mitochondrial adaptor protein MAVS (also known

as IPS1, VISA or CARDIF). Viral RNA triggers a conformational change in RIG-I, leading to MAVS activation and activation

of IKK and TBK1, with subsequent interferon production driven by IRF-3 and NFκB activation and translocation. A remarkable

recent report demonstrated that MAVS forms large prion-like aggregates, which stimulate IFN-I activation in a potent and pro-

longed fashion. This form of signaling, though well known in yeast and fungi, had not previously been reported in eukaryotic

cells. We wondered if the excess type I interferon production in SLE could be due to robust MAVS signaling, and whether

we might be able to detect it using gel electophoresis techniques borrowed from the amyloid/prion field. We have found that

a little over a third of our lupus patients harbor such aggregated MAVS protein in their peripheral blood cells. Aggregated MAVS

is not present in cells from normal subjects. This observation suggests a mechanism for increased type I interferon production,

namely that these aggregates, once formed, are poorly biodegradable, and may thus provide inappropriately prolonged and potent

stimulation of IFN type I production after viral infection or other environmental influences. The basis of MAVS aggregation

in SLE is under scrutiny in our laboratory.

(2010. 1. 1∼2010. 12. 31)


Invited Lecture II


S13

The Utility of Ultrasound in the Detection and Monitoring of Synovitis and Disease Activity in Rheumatoid Arthritis

Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria

Peter Mandl

In the last decades, data from both randomized clinical trials as well as observational studies have firmly established the superior

role of ultrasonography in detecting synovitis in rheumatoid arthritis as compared to physical examination. The development of

ultrasound definitions of pathology as well as the standardization and dissemination of the ultrasonographic acquisition technique

have facilitated the staging of multicenter studies yielding comparable data. These developments have led to improvements in

the reliability of ultrasound, which has shown to be superior to the clinical assessment of synovitis in several recent studies.

Qualitative, semiquantitative and quantitative scoring systems have been developed for the evaluation both grey-scale signs of

synovitis and of the accompanying Doppler signal for individual joints and these may be collated to calculate global scores for

evaluation on the level of the patient. Data from a randomized, prospective multicenter studies have evaluated a large number

of both binary and graded ultrasound-based global joint scoring systems, and have generally revealed that such indices possess

at least as good metrological properties as clinical examination. Prior attempts at measuring disease activity by ultrasound have

been rivaled by recent studies which have evaluated composite disease activity indices, which also included ultrasound data;

these have been shown to improve the reliability of such indices and may have considerable impact on the classification of

patients according to disease activity.

(2010. 1. 1∼2010. 12. 31)


Free Paper Session

J o u r n a l o f R h e u m a t i c D i s e a s e sV o l . 2 0 , S u p p l . 1 , M a y , 2 0 1 3 RA-Pathogenesis (I)

S17

Global Metabolite Profiling of Synovial Fluids from Different Forms of Inflammatory Arthritis for the Identification of Putative

Biomarker in Rheumatoid Arthritis

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine1, School of Life Sciences and Biotechnology, Korea University2, Department of Medicine,

Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine3, Seoul, Korea

Jiwon Hwang1, Sooah Kim2, Jaejoon Lee1, Joong Kyong Ahn3, Eun-Mi Koh

1, Kyoung Heon Kim

2, Hoon-Suk Cha

1

Backgrounds: Metabolite profiling is recently applied in identifying biomarkers in medical research including rheumatologic

diseases.

Aim: To identify putative biomarker for rheumatoid arthritis (RA) compared to the other inflammatory arthritis.

Methods: Synovial fluid samples were obtained from patients with RA (n = 13) and ankylosing spondylitis (AS) (n = 7),

Behcet’s disease (BD) (n = 5) and gout (n = 13). To identify putative biomarkers for RA, the synovial fluid samples were

divided into two groups; RA versus non-RA (NRA). The metabolites were analyzed by gas chromatography/time-of-flight mass

spectrometry (GC/TOF MS). The multivariate statistical analyses by orthogonal partial least squares discriminant analysis

(OPLS-DA) were conducted and the potential biomarkers were evaluated by variable importance for projection (VIP) values,

non-parametric Wilcoxon-Mann-Whitney test and one-way ANOVA test. Chemometric model validation was finally carried out

by receiver operating characteristic (ROC) curve and area under the ROC curve (AUC).

Results: A total of 119 metabolites were identified. The metabolite profiling between RA and NRA were clearly discriminated

by OPLS-DA. Forty-one candidates were selected by VIP scores of greater than 1.0, of which 29 metabolites were elevated

in RA and 12 in NRA. After eliminating variables with no significant difference by Wilcoxon-Mann-Whitney test and one-way

ANOVA test, 23 of 41 metabolites were selected as putative biomarkers. Fifteen metabolites were higher level in RA (succinic

acid, octadecanol, asparagines, etc.) and 8 in NRA (isopalmitic acid, glycerol, myristic acid, etc.). These metabolites were validated

by AUC, all of which had AUC > 0.8. ROC curve analysis for the power of discrimination of RA from NRA showed a sensitivity

of 69.2% and a specificity of 92%.

Conclusion: Our study suggests that the synovial fluid metabolomic profiling can be a novel approach in differentiating RA

from AS, BD and gout. A set of validated metabolites could be a putative biomarker in synovial fluid of RA patients.


S18

Discriminative Metabolite Profiling of Synovial Fluid in Rheumatoid Arthritis Compared to Osteoarthritis

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine1, School of Life Sciences and Biotechnology, Korea University2, Department of Medicine,

Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine3, Seoul, Korea

Jiwon Hwang1, Sooah Kim2, Jaejoon Lee1, Joong Kyong Ahn3, Eun-Mi Koh1, Kyoung Heon Kim2, Hoon-Suk Cha1

Background: Metabolomics is the study of unique chemical imprints that represent specific cellular processes in a cell, tissue,

organ or organism.

Aim: To investigate the metabolites of synovial fluid in patients with RA and OA and to identify characteristic biomarkers

to differentiate two diseases.

Methods: Synovial fluid samples were obtained from patients with RA (n = 18) and OA (n = 11). The extracted metabolites

from synovial fluid were analyzed by gas chromatography/time-of-flight mass spectrometry (GC/TOF MS). The identified metabo-

lites from synovial fluid extracts of RA and OA were then subjected to multivariate statistical analysis by orthogonal partial

least squares discriminant analysis (OPLS-DA): R2 indicates the fitting ability of total variation and Q2 designates the validity

of discrimination. Both have range from 0 to 1, where the higher R2 or Q2 connotes a model with the higher predictive and

discriminative value. Values of variable importance for projection (VIP) greater than 1 from OPLS-DA were used to identify

potential biomarkers and the significance was defined by Welch’s t-test with level of p < 0.01.

Results: Sixty-three metabolites were identified; 20 amino acids, 14 fatty acids, 10 sugars, 7 organic acids, 5 amines and 7

others. The OPLS-DA demonstrated a distinctive metabolite profile of synovial fluid between RA and OA, with the variation

value (R2) of 0.97 and the predictive capability value (Q2) of 0.75. Twenty four metabolites were obtained by VIP values of

greater than 1 and 17 of them were selected as specific biomarkers by Welch’s t-test. Of 17 metabolites, 6 were up-regulated

in RA (maltose, lignoceric acid, uracil, mannitol, pyrophosphate and phosphoric acid) and 11 in OA (lysine, tyrosine, valine,

glyceric acid, alanine, asparagines, hydroxylamine, tryptophan, glycerol, glutamine and citrulline).

Conclusion: Our results demonstrated that metabolite profiling of synovial fluid clearly separates RA from OA. This study

suggests that metabolomics could be a useful diagnostic tool by identifying discriminative biomarkers.


S19

MRP8 Promotes Th17 Differentiation Via Upregulation of IL-6 Production by Fibroblast-like Synoviocytes in Rheumatoid Arthritis

가톨릭 학교 의과 학 내과학교실

정승민ㆍ이재호ㆍ서 선ㆍ고정희ㆍ이주하ㆍ곽승기ㆍ박경수ㆍ박성환

Introduction: Myeloid-related protein (MRP)8/MRP14 is an endogenous Toll-like receptor (TLR)4 ligand and is abundant in

synovial fluid (SF) of rheumatoid arthritis (RA) patients. Belonging to damage associated molecular patterns (DAMPs), it amplifies

proinflammatory mediators and facilitates a wide range of inflammatory and autoimmune diseases.

Objective: We investigated whether the level of MRP8/MRP14 is positively associated with IL-6 and IL-17 levels in RA SF.

Methods: The expression of MRP8/MRP14, IL-6 and IL-17 in SF and synovial tissue from patients with RA and osteoarthritis

(OA) was demonstrated by ELISA and immunohistochemistry, respectively. Human peripheral blood mononuclear cells (PBMC)

and CD4+T cells from healthy donor and RA fibroblast-like synoviocytes (FLS) were cultured in presence of MRP8 or MRP14.

The differentiation of Th17 cells was determined using the coculture system consisting of CD4+T cells and RA FLS. To explore

the downstream signaling pathway associated with MRP8-stimulated increase of IL-6, we used anti-TLR4 antibody and inhibitors

of several signaling molecules.

Results: We found that MRP8/MRP14 level had a significant correlation with IL-6 and IL-17 levels in RA SF. We also observed

that MRP8 induced IL-17 production by PBMC but MRP14 did not. Upon stimulation with MRP8, IL-6 production was enhanced

by RA FLS and was further elevated by coculturing RA FLS with activated CD4+T cells. Moreover, we demonstrated that

MRP8-activated IL-6 production by RA FLS promoted differentiation of Th17 cells by the coculture system. Additionally, IL-6

blockade attenuated Th17 polarization of CD4+T cells in the cocultures. Inhibitor studies revealed that MRP8 increased IL-6

production in RA FLS via TLR4/PI3K/NF-κB and MAPK signaling pathways.

Conclusions: Our results show that MRP8 plays a crucial role in stimulating IL-6 expression by RA FLS and subsequently

promotes Th17 differentiation in RA, suggesting that neutralizing MRP8 level in RA synovium may be an effective therapeutic

strategy in RA treatment.


S20

Coenzyme Q10 Suppresses Autoimmune Arthritis Via Regulation of Th17/Treg Cells

가톨릭 학교 의과 학 내과학교실1, 가톨릭 학교 의과 학 류마티스센터2

이주하1, 주연2, 변재경2, 김은경2, 곽승기1, 박경수1, 조미라2, 박성환1

Objective: Coenzyme Q10 (CoQ10), an essential enzyme in oxidative phosphorylation pathway in mitochondria, has been re-

ported to have anti-arthritic effect. Here, we investigated the molecular mechanism underlying the anti-arthritic effects of CoQ10

in autoimmune arthritis.

Methods: CoQ10 was orally administered to SKG mice which developed arthritis after intraperitoneal zymosan injection and

its in vivo effects were determined. The severity of arthritis was determined by measuring arthritis score and histological

evaluation. Differential expression of proinflammatory cytokines, including IL-17, IL-1β and TNF-α was analysed by

immunohistochemistry. Levels of phosphorylated(p)-STAT3, p-STAT5 and the proportion of Th17, Treg cells after CoQ10 treat-

ment in arthritis model were analysed by immunostaining and flow cytometry. In vitro development of Th17 and Treg cells

was analysed by flow cytometry and real-time polymerase chain reaction (RT-PCR). Osteoclastogenic capacity was analyzed

by quantification of tartrate-resistant acid phosphatase positive multinucleated cells.

Results: CoQ10 ameliorated the arthritic phenotype of SKG mice. The expressions of inflammatory cytokines were reduced

in arthritic joints with CoQ10 treatment. The proportion of IL-17 producing cells and the expression of Th17-related molecules

(CCL20, RORgt) was lower in CoQ10 treated SKG mice than control. In contrast, Foxp3+CD25+ Treg cells were more frequently

observed in CoQ10-treated mice. Consistently, the number of pSTAT3+ CD4+ T cells was reduced in the spleens of CoQ10

treated mice, whereas the number of pSTAT5+CD4+ T cells was increased. CoQ10 also suppressed in vitro Th17 differentiation

and osteoclastogenesis. Finally, the suppressive effect of CoQ10 on in vitro Th17 differentiation and osteoclastogenesis from

human peripheral blood monocyte was also verified.

Conclusion: Our results suggest that CoQ10, which ameliorated autoimmune arthritis by regulating Th17/Treg balance and sup-

pressing osteoclastogenesis, may be a promising therapeutic agent for rheumatoid arthritis.

Journal of Rheumatic DiseasesVo l . 2 0 , Sup p l . 1 , May , 20 13 Osteoclasts and Joint Destruction

S21

Dysregulated Osteoclastogenesis is Related to Natural Killer T Cell Dysfunction in Rheumatoid Arthritis

남 학교병원 류마티스내과1, 남 학교병원 진단검사의학과2, 남 학교 의과 학 약리학교실3, 한양 학교 류마티스병원4

진혜미1ㆍ조 난

1ㆍ김문주

1ㆍ정 주

1ㆍ김재이

1ㆍ이정원

1ㆍ이경은

1

박동진1ㆍ김태종1ㆍ이신석1ㆍ기승정2ㆍ김낙성3ㆍ유 4ㆍ박용욱1

Backgournd and Purpose: Natural killer T (NKT) cells have been implicated in the control of autoimmunity, cancer, and

infectious disease. Furthermore, α-galactosylceramide (αGalCer)-activated NKT cells have the ability to modulate innate and

adaptive immunity. The aim of this study is to investigate the role of NKT cells in osteoclastogenesis and to determine the

mechanism on dysregulation of osteoclastogenesis by NKT cells in rheumatoid arthritis (RA) patients.

Methods: Patients with RA (n=15) and healthy controls (n=15) were enrolled in the study. In vitro osteclastogenesis was per-

formed using peripheral blood mononuclear cells (PBMCs) in the presence of M-CSF and RANKL. PBMCs were cultured in

vitro with αGalCer, and proliferation indices of NKT cells were estimated by flow cytometry. Cytokine and gene expressions

were assessed by RT-PCR and flow cytometry.

Results: In vitro osteclastogenesis was found to be significantly inhibited by αGalCer-activated NKT cells in healthy controls,

but not in RA patients. In vitro proliferative responses of NKT cells to αGalCer were found to be impaired in RA patients,

suggesting that dysregulated osteoclastogenesis in RA is due to NKT cell dysfunction. Transwell coculture experiments showed

that NKT cells inhibit osteoclastogenesis in a cell cotact-independent manner. In addition, anti-resorptive cytokines, such as IFN-γ,

IL-4 and GM-CSF, were produced from αGalCer-activated NKT cells in healthy controls, but not in RA patients. Cytokine block-

ing experiments showed that NKT cells inhibit osteoclastogenesis and down-regulate osteoclast-associated genes, such as TRAP,

CTR, OSCAR and CTSK, mainly through IFN-γ production.

Conclusions: Our study demonstrates that in vitro osteoclastogenesis is negatively regulated by NKT cells through the production

of IFN-γ. The regulation of osteoclastogeneis was found to be impaired in RA patients, which is related to NKT cell dysfunction.

These findings provide important information for the exploration of therapeutic strategies to prevent bone destruction in rheumatoid

arthritis.

Disclosure: This study was supported by grants from the National Research Foundation of Korea Grant funded by the Korean

Government (2011-0011332).


S22

Tubastatin A, A Selective HDAC6 Inhibitor, Suppresses Synovial Inflammation and Joint Destruction in a Collagen

Antibody-induced Arthritis Mouse Model

Department of Medicine, Samsung Medical Center1, Samsung Biomedical Research Institute2, Kangbuk Samsung Hospital3, Sungkyunkwan University School of Medicine, Korea

Jaejoon Lee1, Eun Chung Hong2, In Young Kim1, Hyemin Jeong1, Jiwon Hwang1, Hyungjin Kim¹, Eun-Kyung Bae2, Joong Kyong Ahn3, Hoon-Suk Cha1, Eun-Mi Koh1

Backgrounds: Histone deacetylases (HDAC) play a key role in regulating gene expression by deacetylasing histones, and HDAC

inhibitors induce various cellular effects, including apoptosis, cell cycle arrest and inhibition of angiogenesis. Tubastatin A is

a potent and selective HDAC6 inhibitor and its anti-rheumatic effect has not been determined.

Objectives: To investigate the effect of Tubastatin A on synovial inflammation and joint destruction in collagen antibody-induced

arthritis (CAIA) mouse model.

Methods: CAIA mice were given daily intraperitonial injections of various concentration of Tubastatin A (0, 10, 50, 100 mg/kg,

n=6 each). Clinical score, paw thickness, and body weight were measured for 14 days. On day 15, mice were sacrificed and

the expression of TNF-α, IL-1, IL-6 from the serum was analyzed using ELISA. Hind foot was examined histologically and

micro CT was performed to quantify joint destruction.

Results: In the Tubastatin A-treated group, clinical arthritis was attenuated and paw thickness was lower and this effect was

statistically significant in the Tubastatin 100 mg/kg group compared to control. All mice lost a small amount of weight but

the difference was not statistically significant compared to the control mice. In the Tubastatin A 100 mg/kg group, the histological

severity of synovial inflammation was lower and the joint destruction as quantified by micro CT was significantly attenuated.

Among pro-inflammatory cytokines, expression of IL-6 was significantly lower in the Tubastatin A 50 mg/kg group compared

to control.

Conclusions: Our data demonstrated that Tubastatin A, a selective HDAC6 inhibitor, ameliorates synovial inflammation and

protects against joint destruction in CAIA mice, and reduced expression of IL-6. Our data suggest that Tubastatin A warrant

further investigation as a potential therapeutic agent in rheumatoid arthritis.


S23

Red Ginseng Extract Regulates Regulatory T Cell and Th17 Cell, and Inhibits Osteoclastogenesis in Autoimmune Arthritis

가톨릭 학교 의과 학 류마티스내과학교실

Jae Ho Lee, Jung Hee Koh, Young Sun Suh, Seung-Min Jung, Jennifer Lee, Mi-La Cho, Seung-Ki Kwok, Kyung-Su Park, Sung-Hwan Park

Background: Red ginseng is one of oriental medicines, steam form of genus Panax ginseng C. A. Meyer of the family

Araliaceae. A study has reported that red ginseng has a protective effect to cancer development.

Objective: To investigate the red ginseng extract effect to autoimmune arthritis by suppressing Th17 cell differentiation and

osteoclastogenesis.

Methods: IL-10 knockout mice were divided 2 groups, which are control, and red ginseng 10 mg/kg. Quantification of Cartilage

damages were measured by using arthritis score and special staining. After induced Th17 cell differentiation from CD4+ T cells,

expression of IL-17, Foxp3 were analyzed by flow cytometry and confocal microscopy. Levels of IL-17, RORC, CCR6, Foxp3

and SOCS3 were examined by ELISA. IκBα, ERK, STAT5, STAT3 were examined by western blot. Mice normal bone marrow

cells were cultured in conditions of osteoclast differentiation with or without red ginseng extract. TRAP stain was done to identify

red ginseng extract effects about suppression of osteoclastogenesis.

Results: We showed that groups treated red ginseng extract were significant lower arthritis score than controls. Cartilage was

preserved significantly in red ginseng extract treating group rather than controls, and cartilage preserving effect. The population

of Th17 cells in flow cytometry was decreased according to red ginseng extract increase in dosage. Moreover, CD25+Foxp3+

cells were increased according to elevated halofuginone dose. IL-17 levels decreased according to red ginseng extract dose

elevation. It showed that TRAP+ multinuclear cell count was smaller in groups treated red ginseng extract than control.

Conclusion: red ginseng extract can be novel treatment strategy to rheumatoid arthritis with the distant future.


S24

Anthocyanins Extracted from Black Soybean Seed Coat Suppress Autoimmune Arthritis and Prevent Osteoclast Formation

Division of Rheumatology Department of Internal Medicine The Catholic University of Korea1, Rheumatism Research Center, College of Medicine, The Catholic University of Korea2, Seoul, Korea

Young Sun Suh¹, Dong-Gun Lee², Jung-Won Woo², Seung-Ye Baek², Sung-Min Kim², Seung-Ki Kwok¹, Sung Hwan Park¹

Objective: Anthocyanins are phenolic compounds with powerful antioxidant activities and abundantly present in black soybean

seed coats. Cyanidin-3-glucoside (C3G) is the major component consisting of ~70% of the total anthocyanins. Here, we evaluated

the effects of anthocyanins extracted from black soybean seed coats in suppressing autoimmune inflammatory and destructive

arthritis in mice.

Methods: The effects of anthocyanins extracted from black soybean seed coats on joint inflammation were investigated by

clinical scoring and histologic analysis in collagen-induced arthritis (CIA). Levels of cytokines were analyzed by

immunohistochemistry. The effects of the anthocyanins on osteoclast differentiation were determined by quantifying tartrate-re-

sistant acid phosphatase positive (TRAP+) multinucleated cells. The mRNA levels of various osteoclast-specific markers were

determined by quantitative real-time PCR.

Results: Treatment with anthocyanins extracted from black soybean seed coats suppressed the clinical and histologic signs of

arthritis in CIA. It reduced expression of proinflammatory cytokines such as IL-1β, TNFα, IL-6, and IL-17 in arthritic joints.

It also lowered the oxidative/nitrative stress markers like iNOS and nitrotyrosine in the joints. Furthermore, in vitro treatment

with the anthocyanins prevented osteoclast differentiation in both mice BMM cells and human monocytes.

Conclusion: Anthocyanins extracted from black soybean seed coats suppressed autoimmune inflammatory arthritis and inhibited

osteoclast differentiation in vitro. The anthocyanins including C3G in black beans may be a promising therapeutic agent for

the treatment of joint inflammation and bone destruction in rheumatoid arthritis.

Journal of Rheumatic DiseasesVo l . 2 0 , Sup p l . 1 , May , 20 13 Spondylarthropathies

S25

Clinical Characteristics of Late-onset Ankylosing Spondylitis

경희 학교 의학 문 학원 내과학교실 류마티스내과

김 열ㆍ송 란ㆍ홍승재ㆍ양형인ㆍ이상훈ㆍ이연아

배경 목 : Most ankylosing spondylitis (AS) patients experience their first symptoms prior to age 45. However, symptoms

of AS can develop after the age 45 and the initial manifestations may vary according to the different onset-age subsets. Our

aim was to investigate the clinical features of late-onset AS.

상과 방법: We retrospectively studied the clinical and laboratory features of 380 patients at Kyung Hee University Medical

Centers. These patients were classified into 2 groups based on their age at symptom onset: adult-onset AS (＞16 but ＜45 years;

AOAS); and late-onset AS (≥45 years; LOAS). We compared the differences between the 2 groups.

결과: There were 22 patients (5.8%) with LOAS. LOAS group had more female patients (50.0% vs. 22.1%, P＜0.001) and

less HLA-B27 positivity (77.3% vs. 81.0%, P＜0.001) than AOAS group. While patients with AOAS were more likely to have

low back pain or buttock pain as an initial manifestation, patients with LOAS more often presented cervical spine pain (31.8%

vs. 19.9%, p＜0.001) and the anterior chest wall pain (22.7% vs. 4.5%) than AOAS. The most notable findings of the LOAS

group were higher initial ESR (57.9±30.2 vs. 26.3±23.1 mm/hr, p＜0.001) and more frequent use of TNF-α inhibitors during

the course of the disease (54.5% vs. 37.3%, p＜0.001).

결론: Our results suggest that LOAS has distinctive presenting symptoms and a higher inflammatory burden. With increased

clinical attention to LOAS as a cause of inflammatory arthritis in elderly patients, a timely initiation of disease-specific treatment

can be provided.


S26

Factors and Outcomes of Diagnostic Delay in Korean Patients with Spondyloarthritis

Department of Internal Medicine, Division of Rheumatology, Gachon University Gil Medical Center, Korea

Seo MR, Ryu HJ, Choi HJ, Beak HJ

Objective: To investigate the factors and outcomes of diagnostic delay in Korean patients with spondyloarthritis.

Methods: We performed a cross-sectional, one center study on the patients with spondyloarthritis (SpA) who visited the

Rheumatology clinic. The information was obtained by a standardized interview, medical record review, assessment of disease

activity and Schober test. Mann-Whitney U-test and partial correlation coefficient adjusted by age and treatment duration were

used for statistical analysis.

Results: One hundred and five consecutive patients (81 male and 24 female) were included, 94 (89.5%) axial SpA and 11

(10.5%) peripheral SpA patients. The average age at disease onset was 25.3 ± 10.1 years. The delay from onset of symptoms

to diagnosis was 9.3 ± 8.3 years. Diagnostic delay was more remarkable in axial SpA patients than in peripheral SpA patients

(10.0 ± 8.5 vs. 3.8 ± 3.7 years, p=0.011). Diagnostic delay showed a correlation with BASDAI (r=0.230, p=0.019), BASFI

(r=0.261, p=0.008), Schober index (r=−0.267, p=0.007), and radiographic damage (mSASSS score; r=0.501, p=0.000). Delayed

visit to the hospital and misdiagnosis as having mechanical back pain was associated with diagnostic delay. Presence of peripheral

arthritis, enthesitis or dactylitis as initial symptoms helped diagnose SpA earlier (7.2 ± 6.8 vs. 11.6 ± 9.2 years, p=0.007). There

were no differences in time delay to diagnosis according to the age at onset, sex, HLA-B27, family history or extra-articular

involvement.

Conclusions: Time delay to diagnoses SpA was correlated with worse disease activity, function and radiographic damage. Factors

of diagnostic delay in Korean SpA patients were time delay to visit the hospital, misdiagnosis as having mechanical back pain,

axial SpA, none of peripheral arthritis, enthesitis or dactylitis as initial symptoms.


S27

Phenotype Difference in Familial Ankylosing Spondylitis (AS) Compared to Sporadic AS

Department of Internal Medicine, Eulji University College of Medicine1, Department of Internal Medicine, Seoul National University College of Medicine2,

Clinical Research Institute, Seoul National University Hospital3, Department of Applied Statistics, Dankook University4,

Seoul, Korea

Hye Won Kim1, Hye Rim Choi2, Su Bin Lee2, Won Ik Chang2, Hyun Jun Chae2, Jin Young Moon

2, Jisue Kang

3, Sungim Lee

4, Eun Young Lee

2

To investigate clinical characteristics and incidence of familial form of ankylosing spondylitis (AS) compared to sporadic AS.

We evaluated patients with AS confirmed by modified New York criteria for familial history of spondylarthropathy (one or

more first to third degrees relatives) by ESSG criteria. Phenotypic characteristics including demographic data, clinical features

(advanced features in radiography, psoriasis, inflammatory bowel disease, arthritis, enthesitis, uveitis), presence of HLA-B27, ESR,

CRP and treatments used were obtained. Recurrence risk (number of spondylarthropathy patients/number of familial members)

in relatives of affected AS subjects was drawn.

A total of 207 AS patients (168 males, 39 females, mean age 37.7±13.6 years, mean disease duration 26.2±15.76 months)

were evaluated. Mean age at first symptom was 26.2±15.7 years. 49 (23.6%) out of 207 patients notified familial history of

spondylarthropathy. Out of 2448 family members, 70 patients (43 males, 27 females) of spondylarthropathy were identified.

Recurrence risks in the all AS patients for first, second and third degree family were 4.54%, 1.92% and 1.54%, which increased

in the familial AS patients (16.1%, 5.21%, and 1.54% respectively). ESR (27.8±26.0, 35.7±34.2, p=0.019), CRP (1.26±1.68,

2.37±3.29, p=0.002) at diagnosis , BMI (22.2±2.5, 23.8±3.4, p=0.005) and frequency of oligoarthritis (16.3%, 34.8%. p=0.013)

were significantly lower in familial form. Clinical features were not different between both groups. Female involvement (26.5%,

16.5%, p=0.088), presence of HLA-B27 (93.9%, 82.9%, p=0.057) were tend to be higher in familial AS.

Korean AS patients had 23.6% of familial history. Recurrence risk in the familial AS was highest in the first degree family.

Patients with familial AS showed lower frequency of oligoarthritis, low BMI and lower inflammatory markers.Trends toward

a higher presence of HLA-B27 and the female dominance were observed in the familial form.


S28

The Reliability and Validity of a Korean Translation of the ASAS Health Index in Korean Patients with Ankylosing Spondylitis

Department of Rheumatology, Research Institute of Medical Sciences, Chonnam National University Medical School and Hospital1, Gwangju,

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases2, Seoul, Korea

Jung-Ho Choi1, Kyung-Eun Lee1, Dong-Jin Park1, Yong-Wook Park1, Shin-Seok Lee1, Tae-Hwan Kim2, Tae-Jong Kim1

Objectives: The objective of this study was to develop a Korean version of the original English version of Assessment of

SpondyloArthritis international Society- Health Index (ASAS HI) and to evaluate its reliability and validity in Korean patients

with Ankylosing Spondylitis (AS).

Methods: A total of 30 outpatients (diagnosed as AS or Non-radiographic Axial Spondyloarthritis) were participated. Translation

and cross-cultural adaptation of the ASAS HI was performed according to the Beaton guidelines (Spine 2000;25(24):3186-3191).

The proposed steps contain 5 stages: translation, synthesis of translation, back translation, expert committee review and pre-testing

in a field test. We also evaluated reliability and validity by calculating Cronbach’s alpha and correlation coefficients between

ASAS-HI score and clinical parameters.

Results: Cronbach’s alpha (= 0.67) was acceptable. The correlations among the mean ASAS-HI score and all tools of assessment

on AS was significantly correlated. The correlations between the ASAS-HI score and both erythrocyte sedimentation rate and

C-reactive protein for the criterion validity were positively correlated (all P-values ＜ 0.05). The results of this study showed

that the Korean translation of the ASAS-HI is an efficient tool in terms of its reliability and validity for the measurement of

the disease state in patients with AS.

Conclusions: The Korean version of the ASAS HI could be used in clinical field to assess and evaluate the state of health

in Korean AS patients.

Journal of Rheumatic DiseasesVo l . 2 0 , Sup p l . 1 , May , 20 13 SLE-Pathogenesis

S29

Mucosal-associated Invariant T Cell Deficiency in Systemic Lupus Erythematosus

남 학교병원 류마티스내과1, 남 학교병원 진단검사의학과2, 한양 학교 류마티스병원3

조 난1ㆍ김문주1ㆍ진혜미1ㆍ정 주1ㆍ김재이1ㆍ이정원1ㆍ이경은1

박동진1ㆍ김태종

1ㆍ이신석

1ㆍ기승정

2ㆍ유

3ㆍ박용욱

1

Purpose: To examine the levels and functions of mucosal-associated invariant T (MAIT) and natural killer T (NKT) cells in

rheumatic diseases, to investigate potential relationships between these two cell populations, and to determine the mechanism

responsible for MAIT and NKT cell dysfunctions.

Methods: Patients with SLE (n=54), RA (n=66), Behçet’s disease (n=9), AS (n=21) and healthy controls (HC; n=136) were

enrolled in the study. MAIT and NKT cell levels, cytokine levels of MAIT cells and expression levels of programmed death-1

(PD-1) were measured by flow cytometry.

Results: Circulating MAIT cell levels were significantly lower in SLE and RA patients than in HC. In particular, this MAIT

cell deficiency was more prominent in CD8 and double negative (DN) MAIT cell subsets. SLE patients had significantly lower

circulating NKT cell levels as compared with HC. Spearman’s correlation analysis revealed that MAIT cell deficiency is related

to NKT cell deficiency in SLE patients, but not in RA patients. Notably, IFN-γ+ MAIT cell levels were found to be significantly

lower in SLE patients than in HC, but the levels were similar between RA patients and HC. The percentages of CD69+ cells

in MAIT cells from HCs increased more than 5-fold in response to α-galactosylceramide (αGalCer). In contrast, MAIT cells

from SLE patints did not activate or activated only slightly. Interestingly, the percentages of PD-1 expressing cells in T cell,

NKT cells, and MAIT cells were found to be significantly higher in SLE patients than in HC, but the expression levels of

PD-1 were similar between RA patients and HC. In RA patients, MAIT cell levels were significantly higher in synovial fluid

than in peripheral bood.

Conclusions: Our study demonstrates that MAIT cell levels and functions are defective in SLE patients and these deficiencies

are related to NKT dysfunction and elevated PD-1 expression. In contrast, circulating MAIT cell deficiency in RA patients is

related to accumulation into synovial fluid. These abnormalities possibly contribute to dysregulated mucosal immunity in SLE.

Disclosure: This study was supported by grants from the National Research Foundation of Korea Grant funded by the Korean

Government (2011-0011332).


S30

Human Adipose Derived Mesenchymal Stem Cells Induce the Expansion of Regulatory B Cells and Ameliorate Autoimmunity

in a Murine Model of Systemic Lupus Erythematosus

가톨릭 학교 의과 학 내과학교실1, 가톨릭 학교 류마티스연구센터2, 한양 학교 의과 학 해부학교실3

곽승기1ㆍ박민정

2ㆍ윤지희

3ㆍ조미라

2ㆍ박성환

1

Objective: Human adipose derived mesenchymal stem cells (MSCs) are multipotent cells characterized by immunomodulatory

properties and are therefore considered a promising tool for the treatment of autoimmune diseases. The study was undertaken

to assess the impact of MSCs on the regulatory B cells and their therapeutic effect in an animal model of systemic lupus eryth-

ematosus (SLE).

Methods: We investigated the in vitro effects of MSCs on the population of CD1dhighCD5+ regulatory B cells and/or IL-10

producing B cells production in splenocytes of C57BL/6 mice. Lupus mice (Roquinsan/san mice) were also treated with MSCs,

and serum autoantibodies, histologic changes in the kidney and the population of various B cell and/or T cell subsets including

regulatory B cells in the spleen were analyzed.

Results: Coculture of MSCs with splenocytes from C57BL/6 mice expanded the population of IL-10 producing B cells. It also

expanded the population of CD1dhighCD5+ regulatory B cells. In vivo treatment with MSCs reduced the serum anti-double strand-

ed antibody levels and improved renal pathology of Roquinsan/san mice. MSCs decreased ICOS+CD44+follicular helper T cells,

Th1 cells and Th17 cells in spleens of Roquinsan/san mice. On the contrary, MSCs increased Foxp3 expressing regulatory T

cells. MSCs also decreased the size and number of germinal centers. As expected, in vivo treatment with MSCs expanded the

population of regulatory B cells in spleens of Roquinsan/san mice.

Conclusion: Our results indicate that human adipose derived MSCs induce the expansion of regulatory B cells and ameliorate

autoimmunity in a murine model of SLE. These finding suggest that human adipose derived MSCs be a promising therapeutic

strategy targeting B cell mediated autoimmune disease such as SLE.


S31

CD40 Activated Human CD27-CD38

Int Pre-naive B Cells

Modulate CD4+ T Cell Activation via IL-10 Production

Ewha Womans University School of Medicine1, Department of Anatomy, Seoul National University2

Ji-Hyun Sim2, Hang-Rae Kim2, Jisoo Lee1

B cells mediate humoral immunity through their production of antibodies, but the role they have in regulating CD4+ T cell

responses has only been recently described. Phenotypically distinct populations of regulatory IL-10 producing B cells were de-

scribed in humans, but their ontogenic origin or mechanisms of immune modulation is unclear. In this study, we demonstrated

that normal developmental intermediate CD27-CD38Int pre-naive B cells in human peripheral blood produced IL-10 after stim-

ulation with CD154-L cells. CD40 activated pre-naive B cells expressed costimulatory molecules CD80 and CD86, but failed

to induce CD4+ T cell proliferation during T cell-B cell interaction. Blockade of IL-10 in vitro restored capacity of pre-naïve

B cells to induce CD4+ T cell proliferation. Stimulation by anti-CD3/CD28 activated CD4+ T cells induced differentiation of

Pre-naïve B cells into autoantibody-producing plasma cells. Pre-naïve B cells from SLE patients were refractory to CD40 stim-

ulation and defective in production of IL-10. This inherently unique effector function of pre-naïve B cells to modulate CD4+

T cell activation by auto-regulating accessory cell function via IL-10 production may be an important mechanism in maintaining

peripheral tolerance and prevention of autoimmunity.

Disclosure: This work was supported by Basic Science Research Program through the National Research Foundation (NRF) fund-

ed by the ministry of Education and Technology (2010-0010589).


S32

Delta Neutrophil Index as a Useful Marker for the Differential Diagnosis Between Flare and Infection

in Febrile Patients with Systemic Lupus Erythematosus

연세 학교 의과 학 내과학교실 류마티스내과

하유정ㆍ표정윤ㆍ박진수ㆍ박용범ㆍ이수곤ㆍ이상원

Background: The immature granulocyte count has been reported to be a marker of infection and sepsis. The difference in

leukocyte subfractions (delta neutrophil index, DNI) measured by ADVIA 2120 reflect the fraction of circulating immature gran-

ulocytes in the blood. Since fever is the common symptom of systemic lupus erythematosus (SLE), it is uneasy to discriminate

between SLE flare and infection. In this study, we investigated the usefulness of DNI in discriminating SLE flare from infection

in febrile SLE patients.

Methods: One hundred-eleven episodes of 92 SLE patients admitted with febrile episode were reviewed. DNI was determined

using a specific blood cell analyzer.

Results: The infection group showed higher white blood cell and neutrophil counts and higher levels of CRP and procalcitonin

than the SLE flare group. Complement (C)3 and C4 levels were significantly decreased in the SLE flare group. Patients in the

SLE flare group had significantly lower DNI than those in both infection groups, with and without bacteremia. In multivariate

logistic regression analysis, only DNI was a significant independent factor for the presence of infection (OR 18.9). When we

selected DNI value of 2.8% as the cutoff for infection, SLE patients with DNI ≥2.8% were found to have a higher risk for

infection than those with DNI ＜2.8% (Relative risk 8.48).

Conclusions: SLE patients with infection showed higher DNI than SLE flare group, and febrile SLE patients with DNI ≥2.8%

are likely to have infection. Our findings suggest that DNI might be the useful marker for the differential diagnosis between

SLE flare and infection in febrile patients with SLE.

Journal of Rheumatic DiseasesVo l . 2 0 , Sup p l . 1 , May , 20 13 Drug Therapies

S33

The Concomitant Use of Meloxicam and Methotrexate did not Increase the Risk of Silent Kidney or Liver Damage

in Patients with Rheumatoid Arthritis

연세 학교 의과 학 내과학교실

박희진ㆍ박민찬ㆍ박용범ㆍ이수곤ㆍ이상원

Objectives: We investigated whether the concomitant use of meloxicam and methotrexate might induce kidney and liver damages

in patients with rheumatoid arthritis (RA).

Methods: We enrolled 101 RA patients with normal kidney and liver functions taking meloxicam and methotrexate concomitantly

for more than 6 months. Blood and urine tests were performed. Estimated glomerular filtration rate (eGFR) and liver stiffness

measurement (LSM) were used for evaluating silent kidney and liver damages. Ultrasonography was also performed to exclude

structural abnormalities. We adopted 90 mL/min/1.73 mm2 and 5.3 kPa as the cutoff for an abnormal eGFR and LSM, respectively.

The cumulative doses of medications and the mean weekly dose of methotrexate were calculated.

Results: The mean age (85 women) was 51.9 years. The mean eGFR was 97.0 mL/min/1.73 m2 and the mean LSM was 4.7

kPa. The mean weekly dose of methotrexate was 13.4 mg. The mean weekly dose of methotrexate did not correlate with eGFR

or LSM. The uric acid and the cumulative dose of leflunomide were revealed as the only predictors for abnormal eGFR and

LSM values, respectively. Neither the cumulative dose of meloxicam or methotrexate nor the mean weekly dose of methotrexate

showed the significant odds ratio or relative risk for abnormal eGFR and LSM values.

Conclusion: The concomitant use of meloxicam and methotrexate, especially at a mean weekly dose greater than 15 mg, did

not increase the risk for silent kidney or liver damage in RA patients with normal laboratory results taking methotrexate and

meloxicam concurrently for more than 6 months.


S34

Blood B Cell Counts as Predictor of Early Clinical Response after Rituximab in Patients with Rheumatoid Arthritis

Division of Rheumatology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Korea

You Jae Kim, Bon San Koo, Yong-Gil Kim, Chang-Keun Lee, Bin Yoo

Background: B cell depletion with rituximab is effective for reducing the symptoms and inhibiting the progression of joint

damage in patients with rheumatoid arthritis (RA).

Objectives: We aimed to investigate the potential value of measurement of peripheral blood B cell counts after rituximab therapy

in patients with active RA refractory to anti-tumor necrosis factor inhibitors.

Methods: A total of twenty-seven RA patients whom received more than 1 cycle (two 1-gram infusion) of rituximab were

included in this study. Absolute B cell counts on day 1 and 15 before each rituximab infusion was measured by conventional

flow cytometry. On day 15, peripheral B cell levels below 2.5×106 cells/liter was defined as B cell depletion and the clinical

response was analyzed between the 2 groups; depletion vs. non-depletion. Clinical response at 18 weeks after 1st infusion of

rituximab was measured by Disease Activity Score in 28 joints (DAS28) using the erythrocyte sedimentation rate. The analysis

of B cell depletion with regard to DAS28 and continuous variables were performed using Mann-Whitney test.

Results: The mean age at rituximab treatment was 55±13.8 (25∼83) years and the baseline DAS28 was 6.6±0.9 (4.4∼8.1).

The positive rate of RF and ACPA was 90% (27/30) and 72.2% (13/18), respectively. B cells on day 15 was depleted in 17

(56.7%) patients with median value of B cell counts as 1.2×106 cells/liter [range 0.0∼2.5×106/liter]). Patients in whom B cell

depletion was not achieved showed persistently high DAS28 (4.7±0.6 versus 3.3±1.0 [p=0.007]) by 18 weeks and significant

short duration of B cell depletion time (4.0±2.3 versus 8.2±4.3, months [p=0.008]) than those in depletions.

Conclusions: Data derived from B cell depletion with rituximab in active RA patients suggest that measurement of peripheral

B cell counts on 15th day might provide clinical information on early response and non-depletion of B cells can be used as

a predictive factor of poor response.


S35

Efficacy and Safety of Tacrolimus in Active Rheumatoid Arthritis Patients Shown Unsuccessful Response Against Methotrexate:

Non-Comparative, Single Arm, Multi-Center, Phase 4 Study

Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine of Chonbuk National University Hospital-Chonbuk National University1,

Gyeongsang National University Hospital2, Wonkwang University Hospital

3, Pusan National

University Hospital4, Chonnam National University Hospital

5, Korea

Won Seok Lee1, Sang-Il Lee

2, Myung-Soo Lee

3, Sung-Il Kim

4, Shin-Seok Lee

5, Wan-Hee Yoo

1

Background: Tacrolimus (Prograf®) is a macrolide compound produced by actinomyces, Streptomyces tsukubaensis, and a

proved potent immunosuppressant. It inhibits release of inflammatory cytokine involved in RA development, such as TNF-α,

IL-1β and IL-6 by blocking T-cell activation. It was approved as an anti-RA drug in some patients who has no effects with

other antirheumatic drugs.

Objectives: This phase IV, single arm, non-comparative, multicenter study was conducted to investigate the efficacy and safety

of Tacrolimus administration for 4 months in subjects with active RA who showed unsuccessful response against methotrexate

(MTX).

Methods: A total of 78 RA patients were screened and 56 patients were assigned to receive test drug, Tacrolimus 1.5 mg/day

initially and increased 2.0 mg/day by investigator's decision after 8 weeks. Subjects orally ingested the assigned agents once

a day and visited the clinical center at 2, 4, 8, 12 and 16-week for laboratorial and clinical evaluations. The primary efficacy

variable was the change of ACR20 response from baseline after Tacrolimus administration for 4 months. For the safety assessment,

adverse events (AEs) were recorded at each clinical visit.

Results: ACR 20 response rate was 42.9% (24 out of 56 subjects) in ITT population (n=56) while the ACR 20 response rate

was 51.2% (22 out of 43 subjects) in PP population (n=43). The change from baseline of DAS 28 response rate showed significant

difference in visit 4, visit 5 and visit 7 with the mean change of -0.86, -1.04. and -1.42, respectively in ITT population. Throughout

the treatment period, 37 subjects were reported to experience 71 AEs and 4 subjects left the study because of AEs. A total

of 15 subject experienced treatment-related AEs. No subject died because of AE.

Conclusions: There was significant improvement of ACR response rate and health condition with Tacrolimus in subjects with

active RA who showed unsuccessful response against MTX. This drug also had tolerable safety profile, and be a useful medication

for the treatment of RA.


S36

The Effect of Uric Acid Lowering Therapy (ULT) in Preventing Comorbidity of Gout and Acute Gout Attack, A Retrospective Study

Division of Rheumatology, Department of Internal Medicine, Inha University Hospital

Kowoon Joo, Won Park, Seong-Ryul Kwon, Mie-Jin Lim, Kyong Hee Jung, Hoyeon Joo

Objective: To evaluate the effect of uric acid lowering therapy (ULT) on the development of comorbidities and the frequency

of acute arthritic attacks in gout patients.

Methods: We retrospectively examined data of 158 patients who were diagnosed to have gout according to the American College

of Rheumatology (ACR) criteria. The follow up period was at least 4 years in each patient during the period from January

2002 to December 2012. The patients were divided into 2 groups; those whose mean serum uric acid level (sUA) ＜ 6 mg/dL

(2012 ACR uric acid treatment target) and ≥ 6 mg/dL. Comorbidities of gout such as hypertension (HTN), type II diabetes

mellitus (DM), chronic kidney disease (CKD), cardiovascular disease (CVD), kidney stone and the frequency of acute gout attacks

were compared between the groups.

Results: The frequency of acute gout attacks and the yearly rate of acute attack during ULT period were both higher in the

inadequately treated group compared to the adequately treated group (Table 1). More patients in the inadequately treated group

developed HTN, DM, CVD and kidney stone compared to the adequately treated group (Table 2). The frequency of CKD tended

to decrease in the adequately treated group.

Conclusion: Inadequately treated group was younger with higher BMI and kept lower medication possession rate (MPR). Poorly

treated patients had more gout attacks and higher yearly rate of acute attack. Tight control of uric acid decreased the development

of comorbidities of gout such as HTN, DM, CVD and urinary stone despite the same CVD risk factors.

Journal of Rheumatic DiseasesVo l . 2 0 , Sup p l . 1 , May , 20 13 Fibromyalgia and Miscellaneous

S37

Relationship Between Body Mass Index, Fat Mass and Muscle Mass with Musculoskeletal Pain in Community Residents

Department of Internal Medicine, Armed Forces Capital Hospital¹, Seongnam, Department in Preventive Medicine, Ajou University School of Medicine², Suwon,

Department of Internal Medicine, University Sacred Heart Hospital³, Anyang, Korea

Jong Jin Yoo¹, Seung Hun Lim², Nam Han Cho² and Hyun Ah Kim³

Objective: The association between parameters related to obesity like fat mass and muscle mass and musculoskeletal pain has

never been assessed. The objective of the present study was to evaluate the relationship between body mass index (BMI), fat

mass, muscle mass, and fat/muscle mass ratio and musculoskeletal pain including widespread pain in community residents.

Methods: In the Korean Health and Genome Study, 1530 participants completed pain questionnaire and underwent dual x-ray

absorptiometry calculating body composition. Widespread pain was defined as pain above the waist, below the waist, on both

sides of the body and in the axial region. Three other categories of pain in these analyses were pain in two or more regions

that did not meet the criteria for widespread pain, pain in one region, and no pain. Normal weight metabolically obese (NWMO)

was defined as the presence of more than 3 features of metabolic syndrome and normal BMI. Tests for a linear trend across

categories of pain constellations were performed using Mantel–Haenszel chi-square tests for categorical variables and the F-sta-

tistics from linear regression models for continuous variables.

Result: BMI, fat mass, muscle mass and fat mass/muscle mass ratio were significantly correlated with pain categories, however,

the correlation was only significant among women. The presence of widespread pain was significantly associated with BMI,

fat mass and fat/muscle mass ratio after multivariate analysis, however, the association was significant only among women. The

prevalence of NWMO was 16.4%(12.7% in men, 19.4% in women). Compared to non-obese subjects without metabolic syndrome

features, widespread pain was more common in subjects with NWMO subjects.

Conclusion: Fat mass, muscle mass, and fat/muscle mass ratio as well as BMI and musculoskeletal pain was significantly

correlated.


S38

The Symptom Severity of Fibromyalgia is Associated with Socioeconomic Status, not with Obesity

in Korean Patients with Fibromyalgia

Department of Internal Medicine, Chonnam National University Medical School1, Gwangju, Department of Internal Medicine, Inje University Haeundae Paik Hospital2, Busan,

Department of Internal Medicine, Soonchunhyang University, College of Medicine3, Cheonan,

Department of Internal Medicine, Maryknoll Medical Center4, Busan, Department of Internal Medicine,

Catholic University of Daegu, School of Medicine5, Daegu, Department of Internal Medicine,

School of Medicine, Kyung Hee University6, Department of Internal Medicine, Soonchunhyang University Seoul Hospital7, Hanyang University College of Medicine and the Hospital for Rheumatic Diseases8, Seoul,

Department of Allergy and Rheumatology, Ajou University Hospital, Ajou University School of Medicine9, Suwon, Department of Internal Medicine, Konyang University Medical School10, Daejeon,

Departments of Internal Medicine, School of Medicine, Keimyung University11, Daegu, Korea

Dong-Jin Park1, Shin-Seok Lee

1, Seong-Ho Kim

2, Seong-Su Nah

3, Ji Hyun Lee

4,

Seong-Kyu Kim5, Yeon-Ah Lee6, Seung-Jae Hong6, Hyun-Sook Kim7, Hye-Soon Lee8, Hyoun Ah Kim9, Chung-Il Joung10, Sang-Hyon Kim11

Objectives: The purpose of this study was to determine whether sociodemographic factors including obesity influence symptoms

of Korean patients with FM.

Methods: This study enrolled 343 FM patients recruited from outpatient clinics at 11 medical centers across the Republic of

Korea, and the patients met the classification criteria for FMS proposed by the ACR in 1990. Sociodemographic, clinical, labo-

ratory, and treatment-related data at the time of enrollment were obtained by reviewing the patients’ charts. All patients completed

a set of self-report inventories to assess severity of FM-related symptoms and underwent the TP examination. The self-report

inventories included the Korean version of the FIQ, the BFI, the PCS and MCS of SF-36, the BDI, the State-Trait Anxiety

Inventory, and the Self-Efficacy Scale.

Results: Seventy six patients (22.1%) of total 343 patients were obese based on the definition of BMI ＞25. Obese patients

did not differ from non-obese patients in pain sensitivity to TP palpation and scores of the self-report inventories in the unadjusted

and age-, gender-, symptom duration-adjusted analyses by propensity score matching. However, socio-economic status such as

employment, insurance, and duration of education was associated with the symptom severity of FM. The employed patients showed

more mild symptoms of FM: lower FIQ score (p=0.011), lower BFI score (p=0.013), higher PCS and MCS (p= 0.012 and p=0.005,

respectively), and lower BDI score (p=0.005). The low-income patients showed more severe symptoms of FM: higher FIQ score

(p=0.040), lower PCS and MCS (p= 0.047 and p=0.006, respectively), and higher BDI score (p＜0.000). Patients with ＞ 12

years of education showed lower TP counts (p=0.034), lower BDI score (p=0.007), and lower STAI II score (p=0.045).

Conclusion: In contrary to western patients with FM, our findings have shown that symptom severity of FM was associated

with socio-economic status, not with obesity in Korean patients.


S39

The Significance of Ectopic Germinal Center in Minor Salivary Gland of Patients with Sjögren’s Syndrome

남 학교 의과 학 류마티스내과학교실

Kyung-Eun Lee, Dong-Jin Park, Jeong-Won Lee, Ji Hyoun Kang, Lihui Wen, Tae-Jong Kim, Yong-Wook Park, Shin-Seok Lee

Objective: To investigate whether the presence of germinal center (GC) in minor salivary glands of patients with Sjögren’s

syndrome (SS) is associated with different clinical and laboratory features.

Methods: Minor salivary gland tissue biopsies from 93 SS patients were used to identify GC-like structures and germinal center

was confirmed by CD21-positive follicular dendritic cell networks. Sociodemographic, glandular, and extraglandular manifes-

tations, and laboratory findings including autoantibodies, complement, and immunoglobulin levels, were analyzed. EULAR SS

disease activity index (ESSDAI) and SS disease damage index (SSDDI) were also measured.

Results: GC-like structures were observed in 28 of 93 SS patients (30.1%). Mean focus score was significantly higher in GC-pos-

itive patients than in GC-negative patients. GC-positive patients had higher CRP levels and had higher prevalence of rheumatoid

factor, anti-CCP antibody, and anti-SSA/Ro antibody compared to GC-negative patients. However, glandular and extra-glandular

manifestations were not different between the two groups.

Conclusion: Our findings showed that SS patients who had GC-like structures in minor salivary glands had different laboratory

profiles compared to those patients who didn’t have. Long-term follow-up of these patients will be necessary to see whether

these laboratory abnormalities translate into changes in clinical features.


S40

Figure 1.

The Ratio and Clinical Characteristics of IgG4-related Retroperitoneal Fibrosis Patients Among Idiopathic RPF Patients

울산 학교 의과 학 내과학교실

구본산ㆍ윤다림ㆍ홍석찬ㆍ김유재ㆍ김용길ㆍ이창근ㆍ유 빈

Objective: The purpose of our study was to identify the ratio of IgG4-related retroperitoneal fibrosis patients (RPF) who were

diagnosed as idiopathic RPF and investigate histological and clinical characteristics.

Methods: We retrospectively reviewed the medical records of 39 RPF patients in a tertiary care medical center between January

2000 and December 2011. We identified 17 pathologies which were obtained from biopsy or surgery. Immunostaining of IgG4

and histopatholgic examination was performed in all surgical pathologies according to consensus statement on the pathology of

IgG4-related disease which was recently proposed. Clinical charactreristics were also compared between IgG4-related RPF and

idiopathic RPF.

Results: In a total 17 RPF cases, more than 30 IgG4 positive plasma cells were identified in 8 cases with dense lymphoplasma-

cytic infiltrate, storiform fibrosis, or obliterative phlebitis (IgG4 related RPF), but only a few (≤5) IgG4 positive or IgG4 negative

cases were also identified in 9 cases (idiopathic RPF). Among 8 IgG4-related RPF, highly suggestive and probable features of

IgG4 related RPF in histology were shown in 6 cases. In comparison between IgG4 related and idiopathic RPF, mean C-reactive

protein level in initial laboratory findings of IgG4-related RPF was significantly higher than that of idiopathic RPF (12.14 mg/dL

vs. 5.67 mg/dL, p=0.005). Recurrence rate of IgG4-related RPF (50%) was higher than that of idiopathic RPF (22%) (Figure

1).

Conclusion: We found that IgG4 related RPF according to consensus statement on the pathology of IgG4-related disease was

47% of the patients who had been diagnosed as idiopathic RPF in the past. We could suggest that characteristics of IgG4 related

RPF have some differences from that of idiopathic RPF.

Journal of Rheumatic DiseasesVo l . 2 0 , Sup p l . 1 , May , 20 13 Chondrocytes and Osteoarthritis

S41

Fibronectin Fragment Induces Procatabolic Effects Through TLR-2 and not TLR-4 Signaling Pathway in Human Articular Chondrocytes

한림 학교 의과 학 류마티스내과학교실

Eun Jeong Cheon, Su Jin Park, Hyun Ah Kim

Background/Purpose: Fibronectin fragments (FN-fs) are increased in the synovial fluid of osteoarthritis patients and have a

potent catabolic effect. We investigated whether the 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) regulate cartilage

metabolism through Toll-like receptor (TLR) signaling pathway in human articular chondrocytes.

Method: Human articular chondrocytes were obtained at the time of joint replacement surgery of knee osteoarthritis and cultured

in monolayer. Chondrocytes were transfected with TLR-2 expression plasmid or small interfering RNAs (siRNAs) targeting TLR-2

or TLR-4 and Myeloid differentiation factor 88 (MyD88). In 29-kDa FN-f-stimulated chondrocytes, the relative levels of mRNA

for matrix metalloproteinase 1(MMP-1), MMP-3 and MMP-13 were analyzed by real-time quantitative reverse tran-

scription-polymerase chain reaction. Protein expression levels of MMP-1 and MMP-3 and the regulatory effect of TLR-2 on

29-kDa FN-f-mediated signaling pathways were assessed by immunoblotting. MMP-13 production was measured by ELISA assay.

Result: The expression levels of TLR-2, 3, 4 and 5 in TLR family were remarkably elevated in OA cartilage compared to

normal cartilage. When human chondrocytes were stimulated with various fibronectin fragments, TLR-2 expression was highly

increased by 29-kDa FN-f stimulation. Knockdown of TLR-2 expression using siTLR-2 significantly suppressed 29-kDa FN-f-in-

duced MMPs production in human chondrocytes, while siTLR-4 did not have significant influence. Conversely, overexpression

of TLR-2 enhanced 29-kDa FN-f-stimulated MMPs production. Moreover, we found that knockdown of MyD88, a downstream

adaptor in TLR-2 signaling pathways, led to marked reduction of MMPs production induced by 29-kDa FN-f. 29-kDa FN-f-medi-

ated phosphorylation of IkBa and p38 was inhibited by transfection of siTLR-2. Fluorescence microscopic analysis showed direct

interaction between TLR-2 and 29-kDa FN-f in human chondrocytes.

Conclusion: TLR-2 signaling pathway plays an important role in 29-kDa FN-f-stimulated procatabolic responses of human

chondrocyte.


S42

Association Between Body Composition and Knee Pain and Radiographic Knee Osteoarthritis

in Community Residents in Korea

Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Department of Social and Preventive Medicine, Hallym Research Institute of Clinical Epidemiology,

Hallym University2, Chuncheon, Department of Internal Medicine, Seoul National University Hospital

3, Seoul,

Department of Internal Medicine, Hallym University Sacred Heart Hospital4, Anyang, Korea

I. J. Kim1, D. H. Kim

2, J. Y. Jung

2, Y. W. Song

3, H. A. Kim

4

Objective: Recent report has showed the importance of metabolic effects of obesity in osteoarthritis (OA) beyond weight. The

aim of this study was to examine the association of body composition and knee pain and radiographic knee OA in community

residents in Korea.

Methods: Participants were randomly chosen from the population-based Hallym Aging Study, irrespective of whether they had

knee OA or pain. Demographic data was obtained by questionnaire. Knee pain was assessed using the Western Ontario and

McMaster Universities (WOMAC) Osteoarthritis Index and a 100-mm visual analog scale (VAS). Radiographic evaluations con-

sisted of weight-bearing knee anteroposterior radiographs. Total body fat mass and total lean mass were estimated from bio-

impedance analysis measurements.

Results: The mean age of the 328 study subjects was 72.5 years, and 54.1% were female. Radiographic knee OA and metabolic

syndrome were present in 38.1% and 38.7% of subjects. The mean body mass index (BMI) was 24.8 kg/m2, and the mean

ratio of total fat to lean mass was 0.48. After adjusting for age, sex, BMI and knee OA, total muscle mass was significantly

associated with knee pain severity measured with both pain VAS and WOMAC pain scores. Fat/muscle ratio was significantly

associated with pain measured with WOMAC. There was no significant relationship between radiographic knee OA and total

fat or muscle mass.

Conclusion: These results suggest that body composition, specifically muscle mass, has important implications for the manage-

ment of knee pain.


S43

MicroRNA-558 Regulates the Expression of Cyclooxygenase-2 and IL-1β–induced Catabolic Effects in Human Articular Chondrocytes

한림 학교 의과 학 류마티스내과학교실

Su Jin Park, Eun Jeong Cheon, Hyun Ah Kim

Objective: Cyclooxygenase-2 (COX-2) is a major PGE2 synthetic enzyme and is involved in the pathogenesis of chronic in-

flammation and pain in osteoarthritis (OA). The objective of this study was to directly address whether microRNA (miR)-558

can control the IL-1β-mediated induction of COX-2 and catabolic effects in human articular chondrocytes.

Materials and Methods: Total RNA was extracted from the cartilage tissues of normal and OA donors or cultured human

articular chondrocytes.The expression of miR-558 was quantified by TaqMan assay. To investigate the repressive effect of

miR-558 on COX-2 expression, human chondrocytes and chondrogenic SW1353 cells were transfected with mature miR-558

or an antisense inhibitor (anti-miR-558). The expression of COX-2 protein was determined by Western blot analysis and the

involvement of miR-558 in IL-1β–induced catabolic effects was examined by Western blot analysis and ELISA. Direct interaction

between miR-558 and the putative site in the 3’-UTR of COX-2 mRNA was validated by luciferase reporter assay.

Results: Normal human articular cartilage expressed miR-558, and its expression was significantly lower in OA cartilage.

Stimulation with IL-1β led to a significant reduction in miR-558 expression in normal and OA chondrocytes. IL-1β–induced

activation of MAPK and NF-κB decreased miR-558 expression and induced COX-2 expression in chondrocytes. The over-

expression of miR-558 directly suppressed the luciferase activity of a reporter construct containing the 3’-UTR of human COX-2

mRNA and significantly inhibited IL-1β–induced upregulation of COX-2, while treatment with anti-miR-558 enhanced IL-1β

-induced COX-2 expression and reporter activity in chondrocytes. Interestingly, IL-1β-induced activation of NF-κB and ex-

pression of MMP-1 and MMP-13 was additionally inhibited by miR-558 overexpression.

Conclusion: These findings demonstrated that cartilage homeostasis is influenced by miR-558, which directly targets COX-2

and regulates IL-1β–stimulated catabolic effects in human chondrocytes.


S44

Metabolically Abnormal but Normal Weight, Metabolically Healthy Obesity, and Knee Osteoarthritis:

A Cross-sectional Study in Korean Women

인제 학교 의과 학 해운 백병원 류마티스내과

이성근ㆍ김성호

Background: Metabolically abnormal but normal weight is a body phenotype that is not obese on the basis of weight but

is associated with increased metabolic risk than is metabolically healthy normal weight. Metabolically healthy obesity, despite

increased body weight, is known to be a benign condition in terms of cardiovascular risk.

Objectives: The purpose of this study was to analyze the association between knee osteoarthritis and four body phenotypes

defined by the presence of metabolic abnormality and obesity.

Mehods: This was a cross-sectional study using data from 1494 female participants of the Fifth Korean National Health And

Nutrition Examination Survey. Radiographic knee osteoarthritis was defined as Kellgren-Lawrence grade of ≥2. Metabolically

abnormal state is defined as presence of more than one abnormality in five metabolic factors: waist circumference, serum trigly-

ceride, high density lipoprotein cholesterol, blood pressure, and fasting glucose. Participants were grouped into one of the four

body phenotypes based on the presence or absence of metabolic abnormality and obesity: metabolically healthy normal weight

(MHNW), metabolically abnormal but normal weight (MANW), metabolically healthy obesity (MHO), metabolically abnormal

obesity (MAO).

Results: The prevalence of each body phenotype was as follows: MHNW 55.1%, MANW 30.3%, MHO 4.2%, MAO 10.4%.

Prevalence of knee osteoarthritis was higher in MANW than in MHNW and in MAO than in MHO. MANW and MAO were

characterized by higher age, systolic blood pressure, fasting glucose and insulin resistance compared to MHNW and MHO,

respectively. In multivariable analysis, the association between knee osteoarthritis and the four body phenotype was as follows:

MHNW OR: 1.00 (ref), MANW OR: 1.37 (95% CI 1.07∼1.76), MHO OR: 2.66 (95% CI 1.55∼4.58), MAO OR: 3.35 (95%

CI 2.27∼4.95).

Conclusions: MANW and MAO were more closely associated with knee osteoarthritis than were weight-equivalent metabolically

healthy counterparts suggesting the relative roles of biomechanical and metabolic stress in knee osteoarthritis.

Journal of Rheumatic DiseasesVo l . 2 0 , Sup p l . 1 , May , 20 13 Health Services Research

S45

한국의 종합 병원 외래에서 항-종양괴사인자 α (anti-TNF α) 치료에 한 보험 여 기 을 충족하는

류마티스 염 환자의 비율: 다기 , 비 재 , 찰 연구

한양 학교병원 류마티스내과1, 인제 학교 부산백병원 류마티스내과2, 계명 학교동산병원 류마티스내과3, 가톨릭 학교 성빈센트병원 류마티스내과4, 조선 학교병원 류마티스내과5, 한림 학교 성심병원

류마티스내과6, 가톨릭 학교 서울성모병원 류마티스내과

7, 연세 학교 신 세 란스병원 류마티스내과

8,

인하 학교병원 류마티스내과9, 아주 학교병원 류마티스내과

10, 서울 학교병원 류마티스내과

11,

충남 학교병원 류마티스내과12, 인제 학교 일산백병원 류마티스내과

13, 건국 학교병원 류마티스내과

14,

한양 학교 구리병원 류마티스내과15, 구가톨릭 학교병원 류마티스내과16, 을지 학교병원 류마티스내과17

김 담1ㆍ김동욱2ㆍ김상 3ㆍ김완욱4ㆍ김윤성5ㆍ김 아6ㆍ박성환7ㆍ박용범8ㆍ박 원9ㆍ서창희10

송 욱11ㆍ심승철

12ㆍ윤보

13ㆍ이상헌

14ㆍ이혜순

15ㆍ최정윤

16ㆍ허진욱

17ㆍ유

1

배경 목 : 국내의 종합 병원에서 치료 인 류마티스 염 환자 anti-TNF α 치료의 보험 기 을 만족하는 환자의

비율을 조사하여, 미국, 국, 일본의 사용 허용 기 을 만족하는 비율과 비교하고자 하 다. 한 anti-TNF α 치료 상자

와 실제 anti-TNF α 사용자 간의 차이에 한 이유 등을 분석하고자 하 다.

상 방법: 본 연구는 비 재 , 단면 , 찰 연구로서 20세 이상의 류마티스 염 환자로 본 연구에 자발 으로

동의한 환자 1,700명을 상으로 하 다.

결과: 본 연구는 2011년 12월부터 2012년 8월까지 진행되었으며, 국 17개 종합 병원이 참여하여 총 1,700명의 피험자가

등록되었다. 체 환자 1,700명 여성은 1,414명(83.2%)이었으며. 평균 연령은(±표 편차) 56.6±12.0세, 유병기간은

97.9±91.8개월, 류마티스 인자 양성은 76.8%, 동반질환은 65.2%에서 나타났다. 등록시 기 으로 DAS28에 의한 체 피험

자의 질환 활성도는 remission 413명(24.3%), low disease activity 264명(15.5%), moderate disease activity 800명(47.1%), high

disease activity 223명(13.1%) 다. 등록 당시의 임상 소견을 기 으로 하 을 때, 체 1,700명 한국의 보험 기 을 만족

하는 피험자는 50명(2.9%), 미국의 기 은 202명(11.9%), 일본의 기 은 160명(9.4%), 국의 기 은 155명(9.1%)에서 만족

하 다. 1,700명 anti-TNF α 사용 경험자는 306명(18.0%)이며, 조사 당시 사용자는 224명으로 체 환자의 13.2%이었다.

Anti-TNF α 미사용자 1,394명 anti-TNF α 치료 기 만족 환자는 한국 기 32명(2.3%), 미국 기 148명(10.6%), 일본

기 127명(9.1%), 국 기 126명(9.0%)이었다. Anti-TNF α 미사용자 1,394명의 사용하지 않은 이유를 복 집계하여

살펴본 결과, 경구약물로 치료 가능 1,165명(83.6%), 약제 사용 기간 미충족 213명(15.3%), 경제 이유 37명(2.7%) 등의

순으로 나타났다. anti-TNF α 투여 단한 82명은 부작용25명(30.5%), 임상연구 종료 23명(28.0%), 효과부족19명(23.2%)

등의 순으로 약제를 단하 다.

결론: Anti-TNF α 치료 상에 한 한국보험기 을 만족하는 환자의 비율은 다른 나라의 기 에 비해 하게 낮게

나타났다. 상 환자의 60.2%가 DAS28 기 으로 등증 이상의 높은 활성도를 보이고 있음은 다른 나라의 사용기 에

비해 엄격한 한국의 보험기 에 따라 상 으로 낮은 생물학제제의 사용과 연 이 있을 것으로 추정된다.

Disclosure: 본 연구는 (주)한국얀센의 후원으로 이루어졌다.


S46

Systemic Review: Agreement between Tuberculin Skin Test (TST) and Interferon-gamma Release Assay (IGRA) Blood Test for Latent TB

Screening Among Patients with Rheumatic Diseases

Center for the Evaluation of Value and Risk in Health, The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston Massachusetts1, USA,

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases2, Seoul, Korea

Junhee Pyo1, Dam Kim2, Soo-Kyung Cho2, Sang-Cheol Bae2, Yoon-Kyoung Sung2

Introduction: In this study, we conducted meta-analysis on the level of agreement and positivity rates of LTBI screening tests

prior to use of anti-TNF agents. Then, we further analyzed the difference in agreement according to underlying rheumatic disease

and the prevalence of TB in each country.

Method: OVID-MEDLINE, EMBASE, and Cochrane Library were searched for LTBI screening in patients with rheumatic

diseases, including RA, AS, JIA, and PsA, through Nov 21st 2012. Among 135 literatures retrieved, 18 English original research

articles were selected excluding non-FDA approved method and non-rheumatic disease. Heterogeneity was evaluated using the

Cochran Q statistic. A random effect model was constructed in STATA 10®.

Result: In the pooled analysis, 4,764 patients underwent both TST and one of IGRAs. The positivity of TST, TSPOT, and

QFT-GIT was estimated as 34.7%, 16.1%, and 20.7%, respectively. The agreement between TST and QFT-GIT results in 69.8%

[95% CI: 64.3∼75.3]. The rate of positivity by TST, TSPOT, and QFT-GIT was 35.6%, 15.5%, and 17.5% in low-to-moderate

endemic populations (n=854) and 33.6%, 23.9%, and 30.5% in high endemic populations (n=1,010), respectively. Agreement

percentage was 66.1% and 72.7% in low-to-moderate and high endemic populations, respectively. In RA population (n=1073),

the positivity of TST, TSPOT, and QFT-GIT was 31.3%, 22.2% and 27.3%. The agreement between TST and QFT-GIT was

76.1%. The positivity of TST and QFT-GIT was 22.6% and 4.3% in JIA (n=68) and 56.8% and 26.3% in AS (n=317), Agreement

between TST and QFT-GIT was 66.7% and 54.9% in JIA and AS population, respectively.

Conclusion: Among patients with rheumatic diseases, the screening results of TST and IGRAs are inconsistent across the under-

lying disease and endemic area. Specifically, a lower level of agreement between TST and IGRAs was found among patients

with JIA and AS than RA population. It suggests different strategies need for each patient group to detect LTBI in clinical

settings considering endemic origins.


S47

Current Status of Ultrasound Use in Rheumatology in Korea

Department of Rheumatology, Yonsei University Wonju College of Medicine1, Wonju, Division of Rheumatic and Musculoskeletal Disease and NIHR Leeds Musculoskeletal

Biomedical Research Unit (LMBRU), University of Leeds2, Leeds, UK

Taeyoung Kang1, Richard J. Wakefield

2, Paul Emery

2

Purpose: The use of musculoskeletal ultrasound (US) in rheumatology has rapidly increased over the past decade. US has en-

abled rheumatologists to diagnose, prognosticate and monitor disease outcome. However, no data has been reported about the

status of US use in Korea.

Method: We conducted a web-based electronic survey. Modified Korean version of TUI (Targeted Ultrasound Initiative) ques-

tionnaires was used in this survey.

Results: The total 55 respondents were composed of 43 (81.1%) university hospital doctors, 7 (13.2%) general hospital doctors,

2 (3.8%) private clinic doctors. Most of respondents (94.4%) have dedicated access to at least one US machine. Although 77.8%

of respondents have one diagnostic US machine, 16.7% have 2 US systems used in their department. Seventy five percent of

respondents are using US for diagnosing patients with suspected arthritis. However, 25.0% of respondents said that they are

not using US in suspected arthritis yet. Similarly, 66.7% of respondents are using US to detect synovitis permitting accurate

diagnosis of rheumatoid arthritis. However, US are used less frequently (36.1%) for monitoring patients with rheumatoid synovitis.

Although 38.9% of respondents are using their own standard form, most of respondents (94.4%) have a will to us TUI standard

form for assessing US findings. The OMERACT/EULAR standard scoring was the most frequently used form for assessing

synovitis. Insufficient examination time was the biggest barrier to more frequent use of US in their department. Then, insufficient

US training and insufficient reimbursement followed in order.

Conclusion: US is becoming an essential tool in the management of rheumatology patients through its gradual incorporation

into routine clinical use. Standardized training and education have emerged as an important issue to remove barriers to routine

and more frequent use of US in rheumatology clinical practice in Korea.

Acknowledgement: We would like give thanks to Dr. Kwon, Yongchol and Mrs. Hong, HyunKyung for their support of TUI

projects.


S48

Predictors of Indeterminate INF-γ Release Assay in Rheumatic Diseases

남 학교병원 류마티스내과1, 남 학교병원 진단검사의학과2

정 주1ㆍ김태종1ㆍ김형상1ㆍ김재이1ㆍ김문주1ㆍ진혜미1ㆍ조 난1

이정원1ㆍ이경은1ㆍ박동진1ㆍ이신석1ㆍ기승정2ㆍ박용욱1

Background and Purpose: IFN-γ release assays (IGRA) are increasingly used as an alternative to the traditional tuberculin

skin test for the diagnosis of latent Mycobacterium tuberculosis infection. Imperfect sensitivity of IGRA is a potential problem

prior to using immunosuppressive agents in rheumatic field. Therefore, the aim of our observational study is to investigate factors

associated with indeterminate IGRA results in rheumatic disease.

Methods: A total of 839 patients (RA n=289, AS n=287, SLE n=62, Sjögren’s syndrome n=16, Behçet’s disease n=28, and

others n=193) with rheumatic disease were included. IGRA using QuantiFERON-TB Gold-In Tube test (QFT-GIT; cellestis, UK)

was indeterminate if the result of IFN-γ concentration was ＜ 0.35 IU/mL for baseline-corrected tuberculosis-specific antigens

and ＜ 0.5 IU/mL for the baseline-corrected positive control; ≥0.35 IU/mL and ＜25% of negative control for baseline-corrected

tuberculosis-specific antigens and ＜0.5 IU/mL for the baseline-corrected positive control; or ＞8 IU/mL for negative control.

Predictors associated with indeterminate results were delineated by using univariate and multivariate polytomous logistic regression

analysis.

Results: In total, 58 (6.9%) patients showed indeterminate results on the QFT-GIT assay. Univariate analysis showed that in-

determinate results were significantly associated with the elderly, seasonal variation, ELISA processing method (manual or automa-

tion), specific disease (ankylosing spondylitis or systemic lupus erythematosus), lymphocytopenia, anemia, and medication (NSAID

and sulfasalazine). In multivariate analysis, age over 70 years (OR 4.01, p=0.001), winter season (OR 3.25, p=0.011), automation

of ELISA process (OR 0.21, p=0.001), SLE (OR 6.50, p＜0.001) and anemia (OR 2.48, p=0.028) were significant predictive

factors of indeterminate result on IGRA.

Conclusion: Indeterminate results of QFT-GIT test were not infrequent in rheumatic disease. Care should be considered for

the interpretation with patients with risk factors of indeterminate result.

Journal of Rheumatic DiseasesVo l . 2 0 , Sup p l . 1 , May , 20 13 RA - Clinical Aspects

S49

Inflammatory Burden Predicts Carotid Plaque Progression and Clinical Cardiovascular Disease in Rheumatoid Arthritis:

the Second Year KARRA Cohort Study

Division of Rheumatology, Department of Internal Medicine, Kyungpook National University School of Medicine, Korea

Churl Hyun Im, Sang Hoon Kwon, Jung Soo Eun, Na Ri KimEon Jeong Nam, Young Mo Kang

Background: Carotid atherosclerosis, especially plaque formation, is prevalent in rheumatoid arthritis (RA) patients, which has

been associated with inflammatory burden in a previous study. To evaluate the risks of carotid atherosclerosis progression and

clinical cardiovascular (CV) disease in RA patients and to determine whether RA associated parameters are predictive for these

disorders, we performed prospective cohort study.

Methods: We measured carotid atherosclerosis using ultrasound in 378 RA patients and 158 normal controls at 2 years from

baseline and prospectively determined clinical CV disease in KARRA cohort. Conventional CV risk factors and RA disease activ-

ity and severity markers were analyzed. Areas under the curve of ESR (ESR-AUC) were calculated at baseline (retrograde) and

during 2 years-follow up (prospective).

Results: Mean carotid IMTs were 0.816±0.169 and 0.770±0.133 at 2 years in RA patients and controls (p=0.001). Number

of carotid plaque increased more rapidly in RA patients compared with controls (0.34±0.67 and 0.21±0.52, respectively, p=0.011).

Progression of plaque formation defined by increased number of plaque was significantly higher in RA patients (p=0.015) and

was significantly associated with conventional CV risk factor number at 2 years (p＜0.001) and ESR-AUC for 2 years (p=0.001).

During the 2-year period, clinical CV events occurred in seven patients (1.7%) in RA patients compared with one patient in

controls. New clinical CV disease in RA patients was significantly associated with baseline ESR-AUC (retrograde) and had sig-

nificantly higher number of carotid plaques (p=0.001). Furthermore the incidence of new CV disease was 4.1% among patients

with plaque and 0.4% among patients without plaque (p=0.011).

Conclusions: Carotid plaque progression is strongly associated with time-integrated inflammatory burden and predicts the clinical

CV disease in RA.


S50

류마티스 염 환자에서 고 압이 심 계 험도와 질병경과에 미치는 향

류마티스 염 임상연구센터1, 한양 학교 류마티스병원2, 삼성서울병원3, 구가톨릭 학교병원4, 남 학교병원5, 한양 학교 구리병원6, 충남 학교병원7, 인제 학교 일산백병원8, 동아 학교병원9,

이화여자 학교 의과 학부속 목동병원10, 한림 학교강남성심병원11, 경희 학교병원12

최찬범1,2ㆍ이지 1ㆍ성윤경1,2ㆍ조수경1,2ㆍ고은미3ㆍ김성규4ㆍ김태종5ㆍ김태환2

방소 6ㆍ심승철7ㆍ유 2ㆍ윤보 8ㆍ이성원9ㆍ이신석5ㆍ이재 3ㆍ이지수10

이혜순6ㆍ 재범

2ㆍ정 옥

11ㆍ정원태

9ㆍ차훈석

3ㆍ최정윤

4ㆍ홍승재

12ㆍ배상철

1,2

Korean Observational Study Network for Arthritis (KORONA) 연구자

배경 목 : 류마티스 염 환자들의 심 계 험도가 높고 이에 류마티스 염 질병활성도와 염증이 심 계

험도 증가에 기여함. 하지만, 고 압과 같은 통 인 험인자도 역할을 할 것임. 류마티스 염 환자에서 고 압이

심 계 험도와 질병경과에 미치는 향을 조사하 다.

상 방법: Korean Observational Study Network for Arthritis (KORONA) 코호트에 등록된 류마티스 염 환자들을 상

으로 일반 인 특성, 질병경과지표(DAS28, HAQ, EQ-5D), 통 심 계 험인자를 조사함. 심 계 험도 평가를

해 Systemic Coronary Risk Evaluation (SCORE) 수와 한국인 심 계 험도 수를 계산함. 고 압이 없는 군과 고

압이 있는 군을 비교하 으며 고 압 군 내에서 압조 이 목표에 도달해 있는 군과 높은 군으로 나 어 비교하 다.

결과: KORONA에 등록된 5,376명의 환자 고지 증, 흡연, 압 등의 정보가 락되어 있는 1,144명을 제외한 4,232명의

환자를 상으로 함. 고 압으로 진단 받았거나 압이 높은 (140/90 mmHg 이상) 환자들이 더 나이가 많고 (p＜0.01),

유병기간이 길고 (p＜0.01), 진단지연 기간이 길고 (p＜0.01), HAQ 수가 높으며 (p＜0.01), EQ-5D 수가 낮고 (p＜0.01),

질병활성도가 높고 (p＜0.01), BMI가 높고 (p＜0.01), 고지 증이 많았음 (p＜0.01). SCORE 수와 한국인 심 계 험도

수도 고 압으로 진단 받았거나 압이 높은 환자에서 유의하게 높았음 (p＜0.01). 고 압 환자 군에서 압이 목표에

도달하지 못한 군이 더 나이가 많았고 (p＜0.01), 유병기간은 짧았으며 (p＜0.01), SCORE 수와 한국인 심 계 험도

다 높았음 (p＜0.01). 고 압으로 진단 받았으나 치료 후 압 조 목표에 도달한 군이 비고 압군에 비해 HAQ 수가

높고 (p＜0.01), EQ-5D 수가 낮고 (p＜0.01), 질병활성도가 높고 (p＜0.01), BMI가 높고 (p＜0.01), SCORE 수와 한국인

심 계 험도 수가 높고 (p＜0.01), 고지 증이 많았다 (p＜0.01).

결론: 고 압이 있는 류마티스 염 환자의 심 계 험도가 높았고, 압 조 이 목표에 도달하여도 비고 압군에

비해 그 험도는 더 높았다.

Disclosure: 본 연구는 보건복지부 보건의료기술진흥사업의 지원에 의하여 이루어진 것임(A102065).


S51

Longitudinal Radiographic Analysis of Rheumatoid Wrist: Minimum 7 Year Follow-up

한양 학교 의과 학 정형외과학교실1, 한 병원 정형외과2

이 1ㆍ최완선2ㆍ이창훈1

Introduction: Only a few studies had reported the natural course of rheumatoid wrist. Furthermore, there was no concern about

spontaneous joint fusion in those studies. The purpose of this study was to address the natural course and spontaneous joint

fusion in rheumatoid wrist through minimum 7 year follow up.

Methods: We retrospectively studied 164 patients (213 wrists) who met inclusion criteria; unequivocal diagnosis of rheumatoid

arthritis by a rheumatologist, serial x-ray of the hand and wrist at least 7-year interval, age ＞18 years and ＜65 years at time

of disease onset, available medical record for obtaining a medical history, and appropriate medical treatment for rheumatoid

arthritis. Erosion was assessed by mean changes of modified Larsen score of wrist joints (radioscaphoid joint, radiolunate joint,

midcarpal joint, scapho-trapezio-trapezium joint, distal radioulnar joint). Carpal height ratio and ulnocarpal distance was measured

at initial and final follow up. The difference of parameters was analyzed with Wilcoxon signed rank test.

Results: Larsen score was increased by 0.8 (SD 1.3) in radioscaphoid joint, 0.9 (SD 1.3) in radiolunate joint, 0.6 (SD 1.4)

in midcarpal joint, 0.6 (SD 1.1) in scapho-trapezio-trapezium joint, 1.1 (SD 1.6) in distal radioulnar joint, respectively. Spontaneous

fusion was observed in 8 wrists (3%) in radiocarpal joint and 39 wrists (18%) in midcarpal joint. Carpal height ratio was 0.49

SD (0.05) at initial visit and 0.48 (SD 0.05) at last follow up (p＞0.05). Ulnar carpal translation was not increased significantly

between initial visit (4.6 mm (SD 2.9)) and last follow up (5.7 mm (SD 2.8)).

Conclusion: Radiologic deterioration was more severe in rheumatoid distal radioulnar joint than other wrist joints through mini-

mum 7 year follow up. Spontaneous fusion was developed more frequently in midcarpal joint than radiocarpal joint. Carpal height

ratio and ulnar carpal translation were not differed significantly with appropriate medical treatment.


S52

Elevated Serum Resistin Levels in Rheumatoid Arthritis with Periodontitis

Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine1, Department of Periodontology, School of Dentistry, Seoul National University College of Medicine2, Seoul, Korea

Byoong Yong Choi1, In Ah Choi1, Myeong Jae Yoon1, Hye Jin Oh1, Hye Won Kim1, Sung Hae Chang

1, Eun Young Lee

1, Eun Bong Lee

1, Yong Moo Lee

2, Yeong Wook Song

1

Background & Objective: Epidemiological relationships between rheumatoid arthritis (RA) and periodontitis (PD) have been

revealed recently. However, the pathologic link between RA and periodontitis has remained unclear. Resistin is adipokine which

has been involved in insulin resistance in rodents but its pro-inflammatory properties are known to be superior to insulin resistance‐inducing effects in human. Previous studies suggested that resistin may play a role in RA and periodontitis.

Subjects & Methods: Serum resistin levels were determined by ELISA in 90 RA patients and 45 healthy subjects (2:1 age

and gender matched). Clinical measurement for PD such as plaque index (PI), gingival index (GI), probing pocket depth (PPD)

and clinical attachment levels (CAL) were performed in total subjects.

Results: Although there was no significant difference in resistin levels between total RA patients and healthy controls (median

9.73 vs. 7.35 ng/mL, p=0.14), serum resistin levels were significantly increased in patients with active RA (DAS28≥3.2; n=49,

11.5 ng/mL) compared to patients with inactive RA (DAS28＜3.2; n=41, 7.3 ng/mL) or control group (p＜0.01 and p＜0.05

respectively). In RA patients, serum resistin levels were positively correlated with inflammatory markers such as ESR (r=0.25,

p ＜ 0.05), CRP (r=0.48, p ＜0 .01) as well as DAS28-CRP (r=0.26, p＜0.05). Serum resistin levels were also elevated in

RA patients with anti-CCP compared to those without anti-CCP (11.28 vs. 8.00 ng/mL, p＜0.05). Serum resistin levels were

significantly higher in RA patients with moderate-severe PD (CAL≥3.0) than in those with normal or mild PD (CAL＜3.0)

(11.95 vs. 7.85 ng/mL, p＜0.01).

Conclusions: Elevated serum resistin levels were associated with higher RA disease activity and the presence of moderate-severe

PD, suggesting that resistin may play a role of pathologic cross-link between RA and PD.

(2010. 1. 1∼2010. 12. 31)


Symposium: 한국인 류마

티스관절염


S55

Table 1. CRCRA 세부과제 구성

세부 과제 주요연구내용 수행기 연구 책임자

1

2

3

4

5

한국인 류마티스 염 다기 코호트 구축과 임상, 약물 역학 연구

류마티스 염 진단 후에 한 측지표 연구

류마티스 염 약물치료 황 임상시험을 통한 치료근거 확립

류마티스 염 약물치료의 경제성 평가

류마티스 염 표 진료지침과 환자교육 로그램 개발

한양 학교 류마티스병원

연세 학교 세 란스병원

서울 학교병원

성균 학교

가톨릭 학교 서울성모병원

배상철

이수곤

송 욱

이의경

박성환

류마티스 염 임상연구센터 구성과 목표

한양 학교 류마티스병원, 보건복지부 지정 류마티스 염 임상연구센터

배 상 철

류마티스 염은 뚜렷한 완치 방법이 없는 만성 질환으로 의 손상, 장애뿐 아니라 질환과 동반된 합병증 등은

상당한 사회경제 부담을 야기한다. 2005년 한국인의 질병부담보고서에 의하면 류마티스 염이 질병장애로 인한 부담

순 는 5 로 조사되어 심근경색증이나 우울증을 넘어섰다. 류마티스 염의 임상 증상과 질병 경과는 매우 다양하여

주요 선진국에서는 환자를 상으로 한 코호트를 구축하여 임상, 약물 역학연구와 함께 병인, 진단, 치료, 방에 한

연구에 활용하고 있다.

류마티스 염 임상연구센터(Clinical Research Center for Rheumatoid Arthritis, 이하 CRCRA)는 보건복지부가 지원하는

임상연구센터로서 한국인 류마티스 염의 유병상태와 임상양상을 악하고 임상시험을 통해 표 화된 진료지침을 마

련하여 류마티스 염 환자의 삶의 질 증진과 국민건강 향상에 기여하는 것을 목표로 하고 있다. 연구수행기간은 2008년

11월부터 2015년 3월까지 총 6년 5개월로서 류마티스 염에 한 총 인 임상 연구를 수행하며, 재는 근거창출임

상연구사업단(National Strategic Coordinating Center for Clinical Research, NSCR) 소속으로 되어 있다.

주요 연구내용으로는 한국인 류마티스 염 환자의 임상양상 약물역학 연구를 비롯하여, 진단 후에 한 측

지표, 치료에 있어서의 연구자주도 임상시험, 치료의 경제성 평가, 그리고 표 진료지침 개발 등을 포함하고 있으며,

CRCRA에서는 이와 같은 연구 외에도 다기 공동 임상연구를 수행하기 한 인 자원을 확보하고, 기 간의 network

구축하는 것을 가장 큰 의의로 생각하고 있다.

효율 연구 수행과 연구진의 구성을 하여, 총 5개의 세부과제로 나 었으며 주요 연구내용과 세부과제 수행기 은

Table 1에 표시하 다. 1세부 과제에서는 한국인 류마티스 염 다기 코호트 구축과 임상, 약물역학 연구를 수행하고

자 재 총 5,700여명의 환자 코호트를 구축하고 추 찰을 진행 이며, 이를 이용한 임상연구의 활성화를 도모하기

하여 연구주제 제안회의 등을 통한 연구자들의 참여와 교류 확 에 힘쓰고 있다. 한, 약제 사용의 효과와 안 성을

연구하기 하여 2011년 6월부터 web을 이용하여 생물학 제제 사용 환자를 상으로 registry를 구축하는 한편, 과거에

생물학 제제를 사용했던 환자를 상으로 구축한 후향 코호트를 다기 으로 확 하고자 비 이다. 2세부에서는

류마티스 염 진단 후에 한 측 지표 연구를 목표로 하고 있으며, 조기 류마티스 염 환자 미분화성

염 환자를 상으로 한 질병 진행 측 인자와 지표에 한 연구를 통하여 류마티스 염의 조기 진단과 치료에

도움을 수 있을 것으로 기 된다. 3세부에서는 한국인 류마티스 염 환자의 약물치료 황을 악하고 향 인

연구자주도 임상시험 다기 연구를 통하여 한국인 류마티스 염 환자에게 합한 표 진료지침을 개발할 수 있는

근거를 마련하고자 연구자주도 임상시험 임상연구의 로토콜을 개발하고 수행 이다. 4세부에서는 류마티스 염

S56 배상철: 류마티스 염 임상연구센터 구성과 목표

환자의 경제성 평가 연구를 통하여 국내 임상 실에서 가장 비용효과 인 약물치료의 안을 제안할 수 있을 것으로

기 된다. 5세부에서는 류마티스 염의 임상활성도 평가법, 상진단법, 류마티스 염 치료 약제에 한 표 진료지

침을 마련하고, 약물복용법, 주사법, 생활습 지침 등의 환자교육 로그램을 개발 이다.

이들 수행기 외에도 실질 으로 50여개의 기 이 참여하는 국 network가 구성되었으며, 이를 통하여 지속 으로

신뢰성과 타당성이 높은 류마티스 염의 임상 근거(evidence)를 창출해 나가고있다.

한 춘추계 류마티스학회를 통하여 지속 으로 수행되는 연구과정과 내용을 소개할 정이며, 건 한 비 과 함께 투명한

정보 공유를 통해 모든 연구자와 류마티스 염 환자에게 도움이 될 수 있는 임상연구 network로 발 시켜 나갈 계획이다.


S57

Figure 1. Rheumatoid arthritis co-

hort conducted by CRCRA

류마티스 염 다기 코호트 구축과 임상약물역학연구

한양 학교 류마티스병원, 보건복지부 지정 류마티스 염 임상연구센터

배 상 철

류마티스 염은 장기간 지속되는 만성질환으로 비가역 인 손상과 기능손실 장애를 유발하므로 치료에 한 단기

간의 임상시험만으로는 치료제의 효과와 부작용을 단하는 데 한계가 있다. 한 임상시험은 이미 진행된 활동성질환을

가진 환자만을 상으로 하기 때문에 류마티스 염의 자연경과에서 요한 발병 기의 치료효과에 해 단할 근거

가 부족하다. 이에 주요 선진국에서는 코호트를 이용한 임상약물역학, 질병부담, 병인, 진단, 치료, 방 교육 측면의

연구가 각국 정부 지원과 주도하에 활발히 진행되고 있다. 그러나 나라와 인종에 따라 질환의 임상 특성 치료 환경에

큰 차이가 있으므로 국가별로 고유한 코호트 구축과 이를 이용한 연구가 필요하다.

코호트연구는 특정 집단을 일정 기간 추 하여 특정 요인 폭로 유무에 따른 질병 발생을 비교하는 역학 연구방법으로

많은 시간과 고비용이 요구된다. 국내에서 류마티스 염은 정책결정자나 국민의 질환 인지도가 조하고 연구투자에

한 우선순 가 낮아 많은 비용과 인력이 소요되는 연구 수행이 어려움에 따라 개별연구자 수 에서 비교 소규모의

단일기 코호트 연구가 수행되어 왔다. 그러나 단일기 코호트는 해당 병원에 내원하는 환자가 체 환자를 표하지

못하는 선택비뚤림의 가능성 때문에 연구결과를 체 환자에게 일반화하여 용하는 데 큰 제약이 있으므로 국규모의

체계 인 다기 코호트 구축 필요성이 제기되었다.

류마티스 염 임상연구센터(Clinical Research Center for Rheumatoid Arthritis, 이하 CRCRA)에서는 제1세부과제(주 기

: 한양 학교 류마티스병원) 주도하에 류마티스 염 환자를 상으로 한 국규모의 향 인 다기 코호트

(KORean Observational study Network for Arthritis, 이하 KORONA)와 생물학 제제를 사용한 류마티스 염 환자를 상

으로 한 registry (Korean Registry of Biologics on Rheumatoid Arthritis, 이하 KORBRA)를 구축하여 조사를 수행하고 있다

(Figure 1).

S58 배상철: 류마티스 염 다기 코호트 구축과 임상약물역학연구

KORONA 구축 임상역학 연구

참여기 등록 황

KORONA는 2009년 반 약 6개월의 비과정을 거쳐 2009년 7월부터 환자등록을 시작하 으며 재 27개 주요 학병

원에서 50여명의 연구자가 참여하고 있다. 등록 상은 ACR 분류기 (1987년)을 만족하는 만18세 이상의 환자이며, 2009

년 7월부터 환자등록을 마감한 2011년 12월까지 약 5,400명의 환자가 KORONA에 등록하 다. 등록된 환자는 1년 간격으

로 추 찰을 진행 이며, 재 추 률은 80% 정도에 달한다.

조사항목 자료의 질 리

연구자와 숙련된 연구원이 개별면담을 통하여 병력, 약제 련 유해반응, 기왕력, 수술력 입원력, 검사력, 사회경제학

특성, 체의학사용, 여성력 등을 조사하 고, DAS28산출을 한 VAS측정, joint count 등과 함께 HAQ, EQ5D 등을

측정하 다. 이와 함께 의무기록을 검토하여 약제 처방력(DMARD, NSAIDs, Steroid, 생물학 제제), 액 검사 심 도,

방사선 사진, 골 도 검사의 실시 여부 결과 등을 조사하 다. 추 찰은 류마티스 염 환자들의 주요 outcome

인 재 질병 활성도, HAQ, EQ5D, 류마티스 염 환자의 방 종력, 새로 발생한 동반질환 약제 련 유해반응

등을 조사하여 추 기간의 변화를 찰하고자 하 으며, 4회차 추 부터는 우울증 등 일부 정보를 추가하여 조사 이다.

조사된 정보의 질을 확보하고자 연구원 교육과 정기 인 평가 워크 평가 인증서 발행 등을 통하여 조사방법

을 표 화하 다. 한 1세부과제 총 에서 매년 정기 으로 각 참여기 을 방문하여 audit을 실시하고 있는데 이를

통하여 연구와 련한 제반사항(IRB 심의, 동의서 확보 리, 자료조사 리 등)을 검하는 한편, 수집된 자료의

data validation으로 확보된 자료 리에도 힘쓰고 있다.

연구성과

재까지 KORONA 구축 소개를 비롯하여 한국인 류마티스 염 환자의 특성, 국내 류마티스 염 유병률과 흡연이

나 유 요인 등 발병 험요인, 류마티스 염 환자의 사망 험과 암 발생 험, 류마티스 염 환자의 질병활성도와

삶의 질 건강상태 평가도구를 검정하는 연구 등에 한 성과가 발표되었다. 특히 4차년도에는 발병시기에 따른 신체기

능 비교 연구로 실제 임상 장에서 약제 유해반응에 한 우려 등으로 소극 인 치료가 행해질 수 있는 고령 발병 환자에

한 보다 극 인 치료의 필요성과 진단 후 10년이내 리의 요성을 제기한 바 있다. 한 KORONA는 미국 하버드

학의 Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study (BRASS)와 함께 한국과 미국환자의 해율을

비교하고 이의 연 요인을 밝 진료에 유용한 정보를 제공하고자 공동연구를 수행 이다.

향후 계획

재 신규 환자등록을 마감하고, 등록환자의 추 찰을 지속하고 있으며, 연구의 질 리를 한 기존의 노력 이외에

시스템 정비와 연구자 독려 피드백을 통해 일정 수 이상의 추 률을 확보하고자 노력 이다. 한 확보된 자료를

이용하여 기능소실 장애발생 측인자 분석, 고령 환자 고령 발생 환자 치료의 안 성 치료효과, 심 계질환을

비롯한 동반질환에 한 임상역학연구, 삶의 질에 향을 미치는 요인, 질병활성도 조 에 따른 기능 소실 삶의 질

향, 질환의 상태 결과 정 연구를 지속 수행하는 한편, CRCRA 내 타 세부과제 근거창출임상연구사업단과의

력강화를 통하여 표 진료지침 개발의 근거를 비롯한 공동·공익의 근거를 제공하고, 한국과 미국 일본의 규모

코호트와 공동연구를 수행하여 국가 간 차이와 차이 련 요인을 분석할 정이다.

KORBRA 구축 약물역학 연구

KORBRA는 류마티스 염 치료에 한 생물학 제제의 효과와 안 성을 조사하기 한 연구로 과거에 생물학 제제

를 사용했던 환자를 상으로 한 Retrospective study for Safety and Efficacy of Anti-Rheumatic treatment with biologiCs

(RESEARCh)와 재 생물학 제제 사용을 시작하는 환자들을 상으로 한 BIOlogics Pharmacoepidemiology StudY

(BIOPSY)로 나뉘어진다.

RESEARCh

RESEARCh는 만 18세 이상의 ACR 기 을 만족하는 류마티스 염 환자 항TNF제제를 비롯한 생물학 제제를 사용

한 이 있는 환자를 상으로 한 후향 인 연구이다. 조사항목은 생물학 제제의 사용 황(제제의 종류, 투여방법, 투여간

격 등)과 기본특성, 과거력(BCG vaccination, Tuberculosis, comorbidity, TST), 검사력(Chest X-ray, BMD, Antibody profile),

질병활성도(ESR, CRP, DAS28), 약물력(DMARDs, NSAID, steroid) 결핵 방요법을 포함한 환자의 임상 특성으로 구성

Journal of Rheumatic Diseases Vol. 20, Suppl. 1, May, 2013 S59

Figure 2. Examples of RESEARCh

Figure 3. Examples of BIOPSY-SF

Table 1. Distribution of prescribed biologics at enrollment

Biologics No of patients

Adalimumab

Etanercept

Abatacept

Infliximab

Rituximab

183

138

43

40

15

되었다. 2010년과 2011년 단일 기 을 상으로 RESEARCh I과 RESEARCh II를 수행하여 600여명의 데이터를 구축하 으

며, 유사한 약물코호트인 일본 REAL과 공동연구를 진행하 다. RESEARCh III는 다기 으로의 확 를 목표로 하여, 2012

년부터 웹 기반의 CRF를 비롯한 시스템 개발을 완료하 으며(Figure 2), 참여 기 확 를 한 의 에 있다.

BIOPSY

BIOPSY는 생물학 제제를 시작하는 환자들을 상으로 향 으로 자료를 수집하는 inception cohort로 웹 기반으로

구축한 간략한 형태의 조사 서식(BIOPSY-SF, Figure 3)을 이용하여 리하고 있다. 생물학 제제의 사용 황과 환자의

기본 특성, 과거력, 검사력 질병활성도 등에 한 정보를 연구자 숙련된 연구원이 1:1 개별면담과 의무기록 조회로

S60 배상철: 류마티스 염 다기 코호트 구축과 임상약물역학연구

조사하고 최 등록이 완료된 환자의 추 찰은 약제 별 보험평가 일정에 맞추어 진행하고 있다. 2011년 6월 연구 개시

이후 2013년 4월 재 총 27개 기 에서 41명의 연구자가 참여하여 420명의 환자가 등록되어 있다(Table 1).

연구성과

수행된 RESEARCh I, II 연구와 체계 인 문헌고찰 등을 통하여 항TNF제제 사용의 안 성(항TNF제제사용 환자에서

결핵 발생 증가, 항TNF 제제 투여 latent TB 진단, 항TNF제제에 의한 HBcAb 양성유무와 간기능 이상의 연 성, CKD

환자에서 etanercept 안 성 등), 약제 사용에 한 유 향(tramadol 부작용 발 의 유 향 등) 등에 한 연구결

과를 보고하 다. 한편, 건강보험평가자료를 이용하여 한국인 류마티스 염 환자의 항TNF제제의 지속성이 외국의 결

과와 유사하고, 소화성궤양이 동반되어 있는 경우 항TNF제제 복용이 지속 으로 유지되는 것을 확인하 는데, 이는 소화

성궤양에 한 경구약제의 복용의 어려움으로 인하여 주사제인 항TNF제제를 선호하게 된 것으로 추측되며, 련한 환자

들에게 하나의 유용한 치료방안이 될 수 있는 것으로 사료된다. 한, 한국과 일본의 생물학 제제 코호트인 RESEARCh

와 REAL의 비교연구에서 한국인 류마티스 염 환자와 일본인 환자는 인구학 특성 치료 경향에서 차이를 보 고,

이는 약제의 안 성 결과에 향을 미침을 보고하 다.

향후계획

RESEARCh III를 통해 생물학 제제 사용자에 한 후향 코호트 구축 기존의 RESEARCh I & II 데이터를 바탕으로

한 분석결과 보고를 지속할 정이다. 한편, 생물학 제제의 안 성과 유효성 유지율, 생물학 제제간의 comparative

effectiveness research를 수행하고 미국과 일본의 주요 코호트와 공동연구를 지속하여 유효하고 안 한 치료에 한 근거를

제시할 것이다.

※ 환자등록 추 찰에 참여해 주신 기 연구자(가나다순)

건국 학교병원(김해림, 이상헌), 건양 학교병원(정청일), 경북 학교병원(강 모), 경희 학교병원(이연아, 홍승재), 강

동경희 학교병원(송란, 이상훈), 고려 학교 구로병원(김재훈, 송 규), 고려 학교 안산병원(최성재), 구가톨릭 학교

병원(김성규, 박성훈, 최정윤), 동아 학교병원(이성원, 정원태), 부산 학교병원(김성일), 성균 학교 서울삼성병원(고

은미, 이재 , 차훈석), 성균 의 강북삼성병원(안 경), 순천향 학교 부천병원( 찬홍), 순천향 학교 천안병원(나성

수), 아주 학교병원(김 아, 서창희), 남 학교병원(이충기), 을지 학교병원(신동 , 임미경), 이화여자 학교 목동병

원(이지수), 인제 학교 부산백병원(김동욱, 허민 ), 인제 학교 일산백병원(윤보 , 이주 ), 남 학교병원(김태종, 이

신석), 북 학교병원(류완희), 제주 학교병원(김진석), 충남 학교병원(심승철), 한림 학교 강남성심병원(정 옥), 한

양 학교 구리병원(방소 , 이혜순), 한양 학교 서울병원(김태환, 배상철, 성윤경, 유 , 재범, 조수경, 최찬범)


S61

류마티스 염 진단 후에 한 측 지표 연구

연세 학교 의과 학1, 충남 학교 의과 학2, 경북 학교 의학 문 학원3

이수곤1ㆍ박용범1ㆍ심승철2ㆍ강 모3

　연구의 목표는 조기에 류마티스 염을 정확히 진단할 수 있는 지표를 개발하고, 조기 류마티스 염 환자를 한

우리나라 실에 맞는 가장 좋은 치료 략을 제시하며, 류마티스 염 환자의 후와 련된 험인자를 규명하는

것이다.

　류마티스 염에서 해는 실 가능한 목표이다. 해율을 높이고 약제투여 없는 완 해에 도달하기 해서 조기

진단과 기부터 극 인 치료 략이 필요하다. 발병 1년 이내의 류마티스 염 환자를 상으로 4주 마다 방문하여

DAS28＜2.6을 치료목표로 정하고 목표지향 인 치료를 시행하고 2년 후 치료결과를 분석하 다. 재까지 139명을 등록

하여, 1군 MTX monotherapy 후 step up, 2군 기 MTX 병합, 3군 기 고용량 루코코르티코이드 MTX 병합, 4군 기

TNF 길항제 병합군으로 나 어 47명 탈락하여 최종 으로 92명을 상으로 분석하 다. HAQ은 6개월 째 3, 4군에서 1,

2군에 비해 빠른 호 을 보 으나 이 후에는 각 군 간의 차이를 보이지 않았다. DAS28＜2.6을 기 으로 해 도달율은

1, 2군에 비해 3, 4군에서 6개월 째 높았으나 2년 후에는 차이를 보이지 않았다. 2년 후 체 해 도달율은 체 70%로서

우수한 효과를 보 다. 2년 째 ACR20 반응율은 4군에서 의미(p=0.034)있게 높았다. 방사선학 변화는 각 군에서 큰 차이를

보이지 않았다. 결론 으로 치료 후 6개월 째 빠른 해 도달 율과 HAQ의 호 을 보이고 ACR20 반응율이 우수하 으나

2년 째 HAQ, 해율 그리고 방사선학 변화의 차이가 없으므로 기에 TNF 길항제 병합투여가 우수하다고 볼 수는

없다.

　미분화성 염은 염증성 염이 있으나 특정 염증성 염의 진단 기 에 부합되지 않는 경우를 말한다. 2010년

미국 유럽 류마티스 학회(ACR/EULAR)에서 류마티스 염의 새로운 진단기 을 제시하 는데, 기존에 미분화성

염으로 분류되었던 환자들에 해 이 새로운 진단기 을 용해 보았다. 미분화성 염 환자 102명 36명(35.2%)

는 류마티스 인자(RF) 양성, 30명(29.5%)는 항 CCP 항체 양성이었고, 102명 33명(32.4%)이 2010년 기 으로 류마티스

염으로 진단되었고 그들은 모두 청 양성이었다. 2010년 기 에 따라 RA로 분류된 환자(Group 1) 31명(93.9%)에서

1∼3개의 small joints 침범이 있었고, 청 양성률이 유의하게 높았으며 특히 높은 역가인 경우가 많았다. (Scand J Rheum

2012;41:192-5). 한, 1987년 미국류마티스학회의 진단기 에 의해 류마티스 염으로 진단된 증상 시작이 12개월 이내

인 조기류마티스 염 환자 170명 156명의 환자(91.8%)가 2010년 진단기 으로도 류마티스 염으로 분류되었다.

이 청 음성인 18명 13명(72.2%)이 새 진단기 에는 류마티스 염으로 분류되지 못하여 청 음성 조기 염

환자들은 2010년 진단기 을 용할 때 주의 깊은 찰이 필요하다고 사료된다(Ann Rheum Dis 2012;71:1097-8).

　류마티스 염 환자에서 항-CCP 항체는 류마티스인자에 비해 높은 특이도를 보이면서 민감도는 비슷한 것으로 알려

져 있다. 그러나 최근 활동성 결핵 환자에서 항-CCP 항체가 양성으로 나타남이 확인되었다. 결핵과 비결핵항산균 환자를

상으로 항-CCP 항체 발 유무를 확인하고 항-CCP 항체 생성에 여하는 PADI4 유 자의 다형성을 조사하여 류마티스

인자의 양성률은 결핵 환자군과 비결핵항산균 환자군이 유사하나 항-CCP 항체는 류마티스 염과 결핵 환자군에서만

발견되어 결핵과 항-CCP 항체의 생성이 연 되어 있을 것으로 사료 된다. 결핵군에서 PADI4_89, 90 의 AG/CT genotype은

조군에 비해 통계 으로 의미있게 낮았다(p=0.005, adjusted OR=0.34) 향 후 PADI4와 결핵 감수성의 연 성을 규명하고

한 류마티스 염에서 항CCP항체의 생성 기 을 밝히는 자료로 사용될 수 있을 것으로 단된다.

　최근 류마티스 염 환자에서 심 계 합병증이 주요한 사망 원인으로 보고되고 있다. 실제 류마티스 염 환자에

서 죽상경화가 정상인보다 더 많이 나타남이 보고되고 있다. 류마티스 염 환자를 상으로 2년 추 검사를 시행하고

상승작용을 단하는 표 검사법인 RERI (relative excess risk due to interaction)를 측정하 을 때 ESR-AUC 와 통

S62 이수곤 외: 류마티스 염 진단 후에 한 측 지표 연구

심 험 요소의 수에 해 계산을 하 는데 4.044로 나타났고 likelihood ratio test에서 두 가지 요인을 모두 포함하 을

때 유의성이 있었다. 이를 통해 류마티스 염의 염증 부하에 의한 동맥경화 진행의 험인자 분석하여 경동맥 라크는

ESR-AUC와 통 심 험 요소의 수와 상승작용을 하는 것을 밝혔다. 한 2년 간 추 찰하 을 때 류마티스

염 환자에서 조군보다 경동맥 라크의 진행이 더 많았는데 새로운 라크의 발생에 있어서는 차이가 없었지만 라

크가 있던 사람에 추가로 발생하는 빈도가 유의하게 더 높았다. 이와 함께 심 질환의 발병도 조군에 비해 높게

나타났다. 다만 발병율이 미국에서 발표된 자료에 비해서는 상당히 낮았다. 향 후 향 연구를 통하여 우리나라 임상에

서 사용 가능한 진단 측 모델 확립할 수 있을 것이다. 한, 류마티스 염 환자에서 adipokine과 염증, 인슐린

항성, 경동맥 음 상 죽상경화 간의 연 성에 한 연구를 진행하 다. 192명의 류마티스 염 환자에서 경동맥

음 를 시행하여 총경동맥(common carotid artery, CCA)의 항 계수(resistive index, RI), intima-media thickness(IMT), 죽

상 (plaque)의 갯수와 부피를 측정하 고, 음 를 시행한 당일 검사실 검사를 시행하여 adipokine과 성반응 물질,

지질, HOMA-IR index를 측정하 다. 경동맥 음 상carotid RI는 carotid IMT, 죽상 의 갯수와 부피와 유의한 연 성을

보 다. Leptin/adiponectin 비율은 다른 여러 변수들을 보정해도 HOMA-IR과 연 성을 보 으며, 다른 변수와 HOMA-IR를

보정해도 carotid RI와 독립성인 연 성을 보 다. 이에 류마티스 염에서 죽상경화의 과정에 leptin과 adiponectin이 요

한 역할을 할 것이라고 추정된다(2012 EULAR, APLAR 발표, manuscript submitted).


S63

류마티스 염 치료근거 확립을 한 연구자주도 임상시험 고안 수행

서울 학교 의과 학 내과학교실

송 욱ㆍ신기철

　최근 류마티스 염의 임상 진단방법의 발 과 규모 임상시험을 통한 새로운 치료제의 도입은 류마티스 염의

치유에 획기 인 장을 마련하 다. 하지만, 그동안 국내 류마티스 염의 황에 한 연구는 주로 유병률이나 삶의

질을 심으로 이루어졌으며 치료의 황과 성, 치료 지침 수립에 련된 연구는 부족하 다. 이에 국내 류마티스

염 환자들의 특성에 맞춘 치료 근거를 확립하기 해 국내 연구자주도 임상시험(investigator-initiated trial, IIT)의 요성

과 필요성의 공감 가 형성되었다. 서울 학교병원에서는 류마티스 염 환자에서의 골다공증과 만성 B형 간염을 주제

로 건강보험심사평가원 데이터베이스 자료를 분석하는데 이어 국 임상연구 네터워크를 구축하여 류마티스 염

환자를 상으로 하는 4개의 연구자주도 임상시험을 진행하고 있다. 특히, TNF-α 억제제 치료를 시작하는 만성 B형

간염환자에게 항바이러스제제의 방 사용에 한 임상시험(ENRIcH)을 2012년 하반기에 개시하여 20여 기 의 참여

하에 환자를 모집하고 있다. 이외에도 류마티스 염의 통 조 을 효과 으로 조 하기 한 치료 략, TNF-α

억제제 치료 항류마티스제 병합요법 략을 주제로 한 임상시험들이 개되고 있다. 앞으로 류마티스 염을 주제로

한 IIT가 활성화되기 해서는 학회 류마티스내과 문의들의 지속 인 심과 참여, 연구자간 네트워킹, 그리고 약

제조를 한 여건 개선 등이 필요하다.

　IIT1 장기간 루코코드티코이드를 복용 인 골 도가 낮아진 류마티스 염 여성 환자에서 월 1회 이반드로네이트

의 유효성을 알아보기 한 임상시험(EMBRACE study)

　IIT2 항-TNFα 치료를 시작하는 B형 간염 바이러스(HBV) 표면항원 혹은 항-HBc 항체 양성 류마티스 질환 환자에서

엔테카비어의 HBV재활성화 방을 평가하기 한 무작 배정, 이 가림, 제 3상, 다기 , 연구자 주도 임상시험

(ENRIcH study)

　IIT3 질병 활성도가 낮은 류마티스 염 환자에서 비스테로이드 항염제 단에 따른 통 증상 변화 치료 양상

변화를 평가하기 한 다기 공동, 공개 향 연구자주도 임상시험(NADIR study)

　IIT4 메토트 세이트에 반응하지 않는 류마티스 염 환자를 상으로 타크로리무스 추가요법의 유효성 안정성을

루노미드 추가요법과 비교평가하기 한 무작 배정, 이 맹검, 활성 조 다기 임상시험(PLATINUM-X study)


S64

류마티스 염 약물치료의 경제성평가

성균 학교

이 의 경

S66 이의경: 류마티스 염 약물치료의 경제성평가

S68 이의경: 류마티스 염 약물치료의 경제성평가


S69

류마티스 염 임상진료지침 개발

Division of Rheumatology, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea

박 성 환

S70 박성환: 류마티스 염 임상진료지침 개발

S72 박성환: 류마티스 염 임상진료지침 개발

(2010. 1. 1∼2010. 12. 31)


Special Lectures


S75

A Phosphoinositide 3-kinase (PI3K)-δ, γ Inhibitor in Models of Rheumatoid Arthritis

Division of Rheumatology, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea

Hae-Rim Kim

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovitis and joint destruction. Treatment with bio-

logical agents like TNF inhibitors has improved outcomes, but many patients have inadequate responses. Orally bioavailable small

molecule inhibitors that target signal transduction have emerged as potential alternatives to expensive biologics. Phosphoinositide

3-kinase (PI3K)γ and PI3Kδ are expressed in rheumatoid arthritis (RA) synovium and regulate innate and adaptive immune

responses. We determined the effect of a potent PI3K-δ,γ inhibitor, IPI-145, in two pre-clinical models of RA. IPI-145 was

administered orally in rat adjuvant-induced arthritis (AA) and intraperitoneally in mouse collagen-induced arthritis (CIA).

Efficacy was assessed by paw swelling, clinical scores, histopathology and radiography, and micro-CT. Gene expression and

Akt phosphorylation in joint tissues were determined by qPCR and Western blot analysis. Serum concentrations of anti-type

II collagen (CII) IgG and IgE were measured by immunoassay. T cell responses to CII were assayed using thymidine incorporation

and immunoassay.

IPI-145 significantly reduced arthritis severity in both RA models using dosing regimens initiated before onset of clinical disease.

Of interest, treatment of established arthritis with IPI-145 in AA, but not CIA, decreased arthritis progression. In AA, histology

scores, radiographic joint damage and matrix metalloproteinase (MMP)-13 expression were reduced in IPI-145-treated rats. In

CIA, joint histology scores and expression of MMP-3 and MMP-13 mRNA were lower in the IPI-145 early treated group than

in the vehicle group. The ratio of anti-CII IgG2a to total IgG in CIA was modestly reduced. IL-17 production in response to

CII was decreased in the IPI-145 treated group, suggesting an inhibitory effect on Th17 cell differentiation.

In conclusion, IPI-145 is a novel and potent PI3K-δ,γ inhibitor that attenuates the inflammation and joint damage in two

animal models of RA. PI3K-δ,γ inhibition reduces synovial inflammation and joint destruction through suppression of MMP

expression in joint tissues, decreased autoantibody levels and diminished IL-17 production. By blocking the partially overlapping

activities of two isoforms, it is likely that the benefit would be greater than blocking a single enzyme. These data suggest that

a targeted molecular PI3K-δ,γ inhibitor may be an important new therapeutic option for RA.


S76

Lymph Node Stromal Cells and Lymphotoxin in Immune Tolerance

가톨릭 학교 서울성모병원 류마티스내과

박 경 수

S78 박경수: Lymph Node Stromal Cells and Lymphotoxin in Immune Tolerance

S80 박경수: Lymph Node Stromal Cells and Lymphotoxin in Immune Tolerance


S82

Health Status and Outcomes in RA: Cross-national Comparison Study between South Korea and US

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Section of Clinical Sciences, Division of Rheumatology, Brigham and Women’s Hospital, Harvard Medical School

Yoon-Kyoung Sung

Overview

Rheumatoid arthritis (RA) is the most common systemic autoimmune arthritides, affecting 0.5∼1.0% of general population (1).

Medical evidence has shown significant improvement in RA treatment over the last two decades, making disease remission possi-

ble for many patients. While many health care stakeholders advocate standardized practice guidelines for RA, the patterns of

treatment likely depend on the country, with differences in physicians’ and patients’ preferences, the insurance system, access

to care, and possibly genetics underlying these differences (2,3). This project have examined the differences in disease status,

drug utilization, and outcomes of RA patients living in South Korea or the United States. We used the KORean Observational

study Network for Arthritis (KORONA) database and the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study

(BRASS) database in this comparative study (4,5). The aims and methods for this first set of analyses were described below.

Objectives/Aims

1. To compare the health status of RA patients and drug utilization in two countries, South Korea and United States.

2. To identify whether RA patients in the two countries differ in the prevalence of sustained remission.

3. To compare health-related quality of life (HRQOL) and associated factors of patients with RA between United States and

South Korea.

Patients

KORean Observational study Network for Arthritis (KORONA)

The KORONA was established in July 2009 by the Clinical Research Center for Rheumatoid Arthritis (CRCRA) funded by

the Ministry of Health and Welfare, South Korea (4). KORONA is based on a prospective protocol and standard, defined data

collection instruments. Demographic and clinical features, laboratory and radiologic data, health-related outcomes, treatment side

effects, resource utilization, and health behaviors of the RA cohort patients are recorded in a database. Enrollment started in

July 2009 and completed in December 2011. There are currently 23 South Korean centers participating in this study to ensure

a cohort representative of the full spectrum of patients with RA. Twenty-three institutions, approximately 38% of rheumatologic

departments at tertiary academic hospitals across South Korea, are part of KORONA. The quality control of data collection and

management has been performed through annual monitoring and auditing, training for staff, providing written manuals and a

protocol for standard operation procedures by the CRCRA. Annual follow-up was initiated in July 2010. As of Dec 31 2011,

a total of 5,300 RA patients had been included in KORONA.

The Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study (BRASS)

The BRASS Registry is a large, single-center, prospective and observational cohort of 1,100 RA patients (5). Enrollment for


the registry began in March of 2003 in the Brigham and Women’s Arthritis Centre, which averages over 3,700 RA visits per

year and has minimal turnover in the patient population. The Arthritis Center provides an ideal setting for registry due to its

access to patient electronic medical records for follow-up interviews and medical record review. At the baseline visit and at

each annual follow up visit, the patient’s rheumatologist fills out a form detailing any extra-articular manifestations, infections,

medication changes, 28- joint count and overall disease activity score. A trained staff member interviews the patient and the

patient fills out a self-administered questionnaire. Details of each questionnaire can be found below under data domains. In addition

to the questionnaires, DNA, RNA and serum specimens are also collected. CRP, anti-CCP and RF titers are run on each patient.

Bilateral hand x-rays are collected at baseline, visit 3 and visit 5. At six-month intervals patients are mailed questionnaires inquir-

ing about functional status, medication changes, resource utilization as well as employment status.

Results

Prevalence and Predictors for Sustained Remission in Rheumatoid Arthritis

A total of 465 subjects with remission in 2009 were analyzed, and sustained remission was achieved by 53 of 92 (57.5%) in

BRASS and by 198 of 373 (53.1%) in KORONA. In multivariate analyses, baseline predictors of sustained remission were:

disease duration less than 5 years [odds ratio (OR) 1.96, 95% confidence interval (95% CI) 1.08∼3.58], Modified Health

Assessment Questionnaire (MHAQ) scores of 0 (OR 1.80, 95% CI 1.18∼2.74), and non-use of oral glucocorticoid (OR 1.58,

95% CI 1.01∼2.47).

Quality of Life in Patients with Rheumatoid Arthritis

In the cross-sectional analysis, the mean (standard deviation) of EQ5D score in BRASS subjects was 0.82 (0.16) and that of

KORONA subjects was 0.69 (0.25) (p＜0.001). Disease activity score (DAS) 28 (p＜0.001) and health assessment questionnaire

(HAQ) score (p＜0.001) were inversely associated high QOL in both cohorts and income (p＜0.001) and number of comorbidities

(p＜0.001) were associated with QOL in KORONA. In the longitudinal analysis, mean QOL change of subjects in each cohort

were not different (p=0.169). Only changes in DAS28 and HAQ during 2 years might predict the QOL changes of RA patients

in both cohorts.

References

1. Abdel-Nasser AM, Rasker JJ, and Valkenburg HA. Epidemiological and clinical aspects relating to the variability of rheuma-

toid arthritis. Semin Arthritis Rheum 1997;27:123-40.

2. Hoebert JM, Mantel-Teeuwisse AK, van Dijk L, Bijlsma JW, Leufkens HG. Do rheumatoid arthritis patients have equal

access to treatment with new medicines?: tumour necrosis factor-alpha inhibitors use in four European countries. Health Policy

2012;104:76-83.

3. Orlewska E, Ancuta I, Anic B, Codrenau C, Damjanov N, Djukic P, et al. Access to biologic treatment for rheumatoid

arthritis in Central and Eastern European (CEE) countries. Med Sci Monit 2011;[17:SR1-13.

4. Sung YK, Cho SK, Choi CB, Park SY, Shim J, Ahn JK, et al. Korean Observational Study Network for Arthritis (KORONA):

Establishment of a Prospective Multicenter Cohort for Rheumatoid Arthritis in South Korea. Semin Arthritis Rheum 2011

Dec 7 [Epub ahead of print].

5. Iannaccone CK, Lee YC, Cui J, Frits ML, Glass RJ, Plenge RM, et al. Using genetic and clinical data to understand response

to disease-modifying anti-rheumatic drug therapy: data from the Brigham and Women's Hospital Rheumatoid Arthritis

Sequential Study. Rheumatology 2011;50:40-6.


S84

PPM1A and Its Autoantibody in Ankylosing Spondylitis

울산 학교 의과 학 서울아산병원 류마티스내과

김 용 길

Objective

Autoantibodies have been known limitedly in ankylosing spondylitis (AS), different to other forms of autoimmune disease (AD).

Our study was undertaken to discover autoantibody related with pathogenesis of AS.

Methods

We performed protoarray in sera of various ADs. Among several identified autoantibodies in AS, we choose Ab against PPM1A,

which was verified by ELISA using sera acquired from two independent groups as well as HLA-B27/huβ2-microglobulin trans-

genic rat. Using synovia of AS, rheumatoid arthritis, and osteoarthritis, we performed immunohistochemical staining for PPM1A

and its endogenous effect was determined by gene transfection in the setting of osteoblast differentiation from MC3T3-E1.

Results

In protoarray and ELISA, autoreactivity against PPM1A was dominant in AS among various ADs. Level of anti-PPM1A was

elevated significantly in patients with high grade sacroiliitis and decreased after anti-TNFα treatment. In sera of transgenic rat,

it was also elevated in arthritis-developed rats compare to those without arthritis. Intracellular PPM1A was stained strongly in

AS tissue, and FLAG-PPM1A transfection enhanced the differentiation of osteoblasts, while siRNA transfection suppressed these.

Conclusions

Conclusively, intracellular PPM1A, over-expressed in AS, could enhance the differentiation of osteoblast and high level of an-

ti-PPM1A Ab in AS serum was associated with advanced disease status.

(2010. 1. 1∼2010. 12. 31)


Invited lecture III


S87

Innate Immune Responses and Gut Homeostasis

Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan

Kiyoshi Takeda

Innate immunity has been shown to control antigen-specific adaptive immune responses. In addition, abnormal activation of

innate immunity, due to the breakdown of negative regulatory mechanisms, causes development of several inflammatory disorders,

including inflammatory bowel diseases. Recent evidences have indicated that aberrant helper T cell responses correlate with devel-

opment of rheumatoid arthritis. Therefore, activity of innate immunity is finely regulated at the intestinal mucosal surfaces.

Intestinal mucosa is a unique site, where many numbers of symbiotic microbiota exist. In the intestinal mucosa, there are several

unique subsets of innate immune cells, which orchestrate a peculiar immune response. For example, intestinal CD103+ dendritic

cells have been shown to instruct development of regulatory T cells in the mesenteric lymph nodes and the lamina propria.

We identified CD70+ dendritic cells that show microbiota-dependent induction of Th17 cells in the lamina propria. In addition,

we identified a unique intestinal CX3CR1high CD11b+ CD11c+ cell subset, which we have named regulatory myeloid (Mreg) cells,

that is responsible for prevention of intestinal inflammation through inhibition of T cell responses. These cells inhibit CD4+ T

cell proliferation in a cell contact-dependent manner, and prevent T cell-dependent colitis. The suppressive activity of Mreg cells

is abrogated in the absence of the IL-10/Stat3 pathway. Thus, activity of several unique subsets of innate immune cells is respon-

sible for maintenance of intestinal homeostasis.

(2010. 1. 1∼2010. 12. 31)


Free Paper Session

Journal of Rheumatic DiseasesVo l . 2 0 , Sup p l . 1 , May , 20 13 RA-Pathogenesis (II)

S91

Smoking, The HLA-DRB1 Shared Epitope and ACPA Fine-specificity in Koreans with Rheumatoid Arthritis: Evidence for more than One

Pathogenic Pathway Linking Smoking to Disease

Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea1, Rheumatology Research Group, University of Birmingham, Birmingham, UK2, Kennedy Institute of Rheumatology, University of Oxford, London, UK3

So-Young Bang1, Benjamin A. Fisher2, Muslima Chowdhury3, Hye-Soon Lee1, Jae-Hoon Kim1, Peter Charles3, Patrick Venables3, Sang-Cheol Bae1

Objectives: Data from North European rheumatoid arthritis (RA) populations has suggested a particularly strong association of gene-en-

vironment interaction between smoking and HLA-DRB1 shared epitope (SE) with antibodies to citrullinated α-enolase and vimentin

peptides. We investigated this further by examining antibodies to citrullinated peptides/proteins (ACPA), ‘fine specificity’ in a Korean

cohort, where there are notable differences in the RA-associated HLA-DRB1 alleles.

Methods: Antibodies to fibrinogen (cFib), α-enolase (CEP-1) and vimentin (cVim) peptides and cyclic citrullinated peptide (CCP)

were measured in 513 cases. The Mann Whitney U Test was used to compare antibody levels. Logistic regression generated odds ratios

for RA in a case-control analysis with 1101 controls. Association of ACPA status and erosion in RA patients was examined by logistic

regression.

Results: Anti-CCP, CEP-1, cVim and cFib were found in 86.7%, 63.9%, 45.5% and 74.7% respectively. The number of ACPA and their

levels were associated with SE, with evidence of a gene-dosage effect. There was a particular association of smoking with levels of an-

ti-CEP-1. However, a gene-environment interaction was associated with all the ACPA positive subgroups (Fig 1). In the absence of SE,

smoking only conferred risk for anti-CCP negative subsets. The presence of erosions was not associated with the number of positive

ACPA or specificity.

Conclusions: The SE governed the magnitude and diversity of the ACPA response, but its interaction with smoking did not exclusively

segregate with any of the ACPA specificities studied here. Smoking was associated with RA by SE-dependent and independent effects.

SYB and BAF are joint first authors. BAF and SCB are joint corresponding authors.


S92

DICAM Inhibits Angiogenesis Via Suppression of AKT and p38 MAP Kinase Signaling

Laboratory for Arthritis and Bone Biology, Fatima Research Institute1, Department of Internal Medicine, Daegu Fatima Hospital2, Daegu, Korea

Seung-Woo Han1,2

, Youn-Kwan Jung1, Eun-Ju Lee

1, Hye-Ri Park

1, Gun-Woo Kim

1,2

Aims: Dual Ig domain Containing Adhesion Molecule (DICAM), a protein with homology to the junctional adhesion molecule

family, has been demonstrated to interact with integrin αVβ3 that plays a critical role in angiogenesis. Here, we determined

the role of DICAM during angiogenesis and the molecular mechanisms involved in the inhibition of angiogenesis.

Methods and Results: DICAM was expressed on the endothelial cells of large vessels to small capillaries. In human umbilical

vein endothelial cells (HUVECs), DICAM was up-regulated by vascular endothelial growth factor (VEGF) through the MEK/ERK

and PI3K/AKT pathways. Furthermore, the exogenous expression of DICAM in HUVECs suppressed angiogenesis in vitro

Matrigel and in vivo plug assays, and conversely, DICAM knockdown enhanced angiogenesis. In addition, DICAM inhibited

HUVEC migration and accelerated apoptosis via down-regulation of Bcl-2, but did not affect viability or proliferation of HUVEC.

Mechanistically, the exogenous expression of DICAM suppressed VEGF-induced phosphorylarion of AKT and p38 MAP kinase.

When integrin signaling was activated by vitronectin, a forced expression of DICAM attenuated integrin β3/FAK signaling and

downstream AKT and p38 MAP kinase signaling in HUVECs.

Conclusion: Collectively, DICAM suppressed angiogenesis by attenuating AKT and p38 MAP kinase signaling, which suggests

that DICAM may be a novel negative regulator of angiogenesis.


S93

Interleukin-33 Acts as a Transcriptional Repressor and Extracellular Cytokine in Fibroblast-like Synoviocytes in Patients with Rheumatoid Arthritis

서울아산병원 의생명연구소 근골격계연구단1, 양산 부산 학교병원 류마티스내과2, 울산 학교 의과 학 서울아산병원 내과학교실 류마티스내과3

이은주1ㆍ소민욱

2ㆍ김용길

3ㆍ유 빈

3ㆍ이창근

3

The aim of this study was to assess the functions of interleukin (IL)-33 in the fibroblast synoviocytes (FLS) of rheumatoid

arthritis (RA) patients. IL-33 and soluble ST2 were measured in plasma samples obtained from patients with RA and osteoarthritis

(OA) using an enzyme-linked immunosorbent assay. Messenger RNA (mRNA) levels of proinflammatory mediators, matrix metal-

loproteinases (MMPs), and receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL) were measured in IL-33-

and anti-ST2-treated RA FLS. To evaluate whether IL-33 regulates osteoclastogenesis, IL-33-stimulated human CD14+ monocytes

and human CD14+ monocytes cocultured with IL-33-stimulated FLS were stained with tartrate-resistant acid phosphatase (TRAP).

RA FLS were also transfected with IL-33 small interfering RNA(siRNA) or plasmids, and changes in the expression and regulation

of NF-κB were determined using Western blot analysis and reporter gene assays. The concentration of IL-33 was higher in

plasma samples obtained from RA patients than OA patients. The expression levels of the IL-33 and ST2 transcripts were elevated

in RA FLS that had been stimulated with poly I:C, IL-1β, and TNF-α. Stimulating RA FLS with exogenous IL-33 increased

RANKL and IP10 mRNA expression, which was blocked by anti-ST2 treatment, and IL-33 directly stimulated the formation

of TRAP+ multinucleated osteoclasts. Silencing IL-33 increased the levels of proinflammatory molecules and MMPs, promoted

the degradation of IκBα, and increased NF-κB activity; these effects were reversed in IL-33 plasmid-transfected FLS. In

conclusion. IL-33 is a dual-function protein that acts as a novel transcriptional repressor of NF-κB and demonstrates extracellular

effects on osteoclastogenesis in RA FLS.


S94

Serum Dickkopf-1/R Spondin-1 Ratio is a Novel Biomarker for Wnt Signaling Status in Patients with Rheumatoid Arthritis

Department of Internal Medicine, Seoul National University Bundang Hospital1, Seongnam, Department of Internal Medicine, Seoul National University Borame Medical Center2,

Department of Internal Medicine, Seoul National University College of Medicine3, Seoul, Korea

Byoong Yong Choi1, Hyon Joung Cho1, Eun Ha Kang1, Kichul Shin2, Yeong Wook Song3, Yun Jong Lee1

Objectives: Recently, R-spondin 1 (Rspo-1) was reported to prevent joint structural change by antagonizing Dickkopf-1 (Dkk-1) in a

murine arthritis model. We investigated the clinical implications of serum Rspo-1 levels and Dkk-1/Rspo-1 ratios in patients with rheuma-

toid arthritis (RA).

Methods: Dkk-1 and Rspo-1 levels were measured in 100 RA patients, 60 ankylosing spondylitis (AS) patients, and 53 healthy controls.

Additionally, those levels were determined before and 12 weeks after anti-TNF-α treatment in 15 RA and 10 AS patients. Clinical varia-

bles were obtained and disease activity indices were calculated; the DAS28 for RA and the AS disease activity score for AS patients.

Radiographic joint damage was assessed by the modified Sharp/Van der Heijde score (SHS) in RA patients.

Results: Compared to controls, serum Rspo-1 levels were significantly lower whereas Dkk-1 levels and Dkk-1/Rspo-1 ratios were sig-

nificantly higher in RA (all p＜0.0001). Dkk-1/Rspo-1 ratios were higher in erosive RA than non-erosive RA (p＜0.05). RA patients with

high Dkk-1/Rspo-1 ratios had significantly higher acute phase reactant levels, DAS28, and total SHS scores (all p＜0.05) than those with

low ratios while Dkk-1 levels did not reflect RA disease activity or joint damage status. After anti-TNF-α treatment of RA patients,

Dkk-1/Rspo-1 ratios and DAS28 were significantly decreased (p=0.001) but Dkk-1 levels did not change.

Conclusions: Serum Dkk-1/Rspo-1 ratio was significantly associated with both disease activity and radiographic change. Our results

suggest that serum Dkk-1/Rspo-1 ratio is a better indicator than Dkk-1 level for evaluating Wnt signaling status in RA patients.

Journal of Rheumatic DiseasesVo l . 2 0 , Sup p l . 1 , May , 20 13 TNF Inhibitor-related Issues

S95

Figure 1. Figure 2.

Mortality in Patients with Rheumatoid Arthritis-associated Interstitial Lung Disease Treated with an Anti-tumor Necrosis Factor Agent

울산 학교 의과 학 내과학교실

구본산ㆍ김유재ㆍ소민욱ㆍ김용길ㆍ이창근ㆍ유 빈

Objective: The purpose of our study was to identify the mortality rate and the causes of death in Rheumatoid arthritis-associated

interstitial lung disease (RA-ILD) patients treated with anti-tumor necrosis factor (anti-TNF).

Methods: We retrospectively reviewed the medical records of RA-ILD patients in a tertiary care medical center between 1995

and 2011. We searched for RA-ILD patients who were treated with anti-TNF agent and analyzed their clinical characteristics.

To determine the effect of anti-TNF therapy on mortality, the patients were divided into DMARDs (disease modifying anti-

rheumatic drug) group and the anti-TNF group.

Results: Twenty four RA-ILD patients treated with anti-TNF agent were analyzed. All six deaths occurred within 14 months

after treatment initiation, and the causes of their deaths included acute exacerbation of ILD, pneumonia, septic shock, and diffuse

alveolar hemorrhage. Survival rate of the patients who started anti-TNF therapy at under 70 years of age was higher than that

of patients 70 years of age or older (Figure 1). In a total 100 RA-ILD patients of our study cohort, the DMARDs group and

the anti-TNF group were composed of 76 and 24 patients, respectively. There were 13 and six deaths, respectively, in the

DMARDs group and the anti-TNF group (17% vs. 25%). The survival rate was not significantly different between the two groups

(p=0.935) (Figure 2).

Conclusion: Although the mortality rate of the patients who underwent anti-TNF therapy was not different from that of patients

treated only with DMARDs, anti-TNF agent should be used with caution in older RA-ILD patients.


S96

Drug Survival Rates of Anti-Tumor Necrosis Factor Therapies in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis

남 학교 의과 학 류마티스학교실

Jeong-Won Lee, Dong-Jin Park, Kyung-Eun Lee, Ji Hyoun Kang, Lihui Wen, Tae-Jong Kim, Yong-Wook Park, Shin-Seok Lee

Objectives. To investigate the drug survival of anti-TNF agents (anti-TNF) in Korean patients with RA and AS and find potential

predictors associated with treatment discontinuation.

Methods: This study included 114 RA patients and 310 AS patients who were treated with anti-TNF agents in a single tertiary

center for at least one year from December 2002 to November 2011. Demographic, clinical, laboratory, and treatment-related

data at the time of initiation of anti-TNF were collected, and the cause of discontinuation was also obtained by reviewing patients’

charts. Survival curves were plotted to compare the drug survival between three different anti-TNF, and life-table analysis and

multivariate Cox proportional hazard models were used to assess predictors of treatment discontinuation of anti-TNF therapy.

Result: Of the 114 RA patients, 64 patients (56.1%) discontinued their first anti-TNF with mean duration of 18.1 months.

In constrast, 65 of 310 patients (21.0%) discontinued their first anti-TNF with mean duration of 84 months. Over a mean follow-up

of 33.8 months (range, 10∼77 months), 1-year and 4-year drug survival rates in RA patients were 44% and 37%, and those

in AS patients were 79% and 67%, respectively. Although survival rate was not different among 3 anti-TNF in AS patients,

in RA patients, etanercept group had a lower discontinuation rate compared with the infliximab group and discontinuatoin rate

between the adalimumab group and the infliximab group was not different. RA patients receiving corticosteroids in combination

with anti-TNF were more likely to discontinue their anti-TNF therapies. Male gender and complete ankylosis on radiographs

of sacroiliiac joint were independent predictors of drug discontunuation in AS paintes.

Conclusion: The drug survival rate of anti-TNF differed between RA and AS patients, with etanercept having the best retention

rate in RA patients and shorter drung survial in RA patients. Our study provides further evidence that real-life treatment of

RA and AS patients may be different from that of randomized clinical trials.


S97

강직성 척추염에서 종양괴사인자 차단제의 도량학 효과에 한 측 인자

경북 학교병원 의과 학 내과학교실

남언정ㆍ권상훈ㆍ은종수ㆍ김나리ㆍ임철 ㆍ강 모

목 : 종양괴사인자 차단제는 강직성 척추염 치료약제 유일하게 척추염증을 감소시킨다고 알려져 있으나, 이에 의한

도량학 효과(metrology outcome)에 한 측인자는 잘 알려져 있지 않다. 이에, 본 연구에서는 강직성 척추염 환자들을

상으로 종양괴사인자 차단제의 도량학 효과를 측할 수 있는 인자에 하여 조사하 다.

방법: 강직성 척추염 환자 33개월까지 종양괴사인자 차단제로 치료받은 116명을 상으로 하 다. 이들 96명은

한 가지, 19명은 두 가지, 그리고 1명은 세 가지 약제를 사용하여, 총 137 를 분석하 다. 치료시작 , 3개월 후, 이후에는

매 6개월마다 추 찰하 다. 약제 효과의 척도로 ASAS20, ASAS40, ASAS5/6, BASDAI50, 그리고 성반응단백(CRP과

ESR)을 이용하 으며, 도량학 효과의 척도로 BASMI, chest expansion을 측정하 다.

결과: 아달리무맵이 62 (45.%), 에터 셉터은 60 (43.8%), 인 리시맵은 15 (10.9%)에서 사용되었으며 세 약제는 비슷

한 약제효과를 나타내었다. ASAS20을 만족하는 경우는 치료 3개월 후 87.3%, 9개월 후 90.3%, 15개월 후 91.6%, 21개월

후 90%, 27개월 후 82.6%, 그리고 33개월 후 90.7% 다. 종양괴사인자 차단제는 치료 3개월 후부터 33개월까지 BASMI,

chest expansion 등의 도량학 척도를 유의하게 호 시켰다. 특히, 치료 3개월 후 ASAS20를 만족하는 환자군(ASAS20

만족군)에서는 33개월까지 지속 으로 도량학 효과가 찰되었으나, ASAS20 비만족군에서는 체 추 찰 동안에

유의한 도량학 효과가 없었다. 치료 3개월 후 ASAS40, ASAS5/6, 그리고 BASDAI50을 만족하는 군과 비만족군을 상으

로 도량학 효과를 분석하 을 때, 두 군간의 도량학 효과 차이는 없었다. ASAS20 만족군에서 BASMI는 치료 3개월

후 가장 호 되었고 (치료 3.8±0.3 vs. 3개월 후 3.0±0.3, p＜0.001) 9개월까지 지속 으로 호 되었으나 (2.7±0.3, p

＜0.001) 이후에는 비슷한 수 을 유지하 다. BASMI 호 과 ASAS20 요소(BASDAI-morning stiffness, BASFI, patient’s

global assessment, pain) 호 사이의 상 계를 분석한 결과, BASMI 호 은 BASDAI-morning stiffness BASFI 호 과

치료 33개월까지 지속 으로 하게 련되어 있었다.

결론: 치료 3개월 후 ASAS20 만족 여부가 종양괴사인자 차단제의 도량학 효과에 한 측인자이었으며, 가역 인

도량학 효과는 치료 9개월 이내에 결정됨이 찰되었다.


S98

TNF 길항제가 응이 되는 류마티스 염 환자들의 임상양상

한림 학교 의과 학 류마티스 내과학교실

손경민ㆍ김범 ㆍ문소 ㆍ서 일ㆍ정 옥ㆍ김인제ㆍ이성연ㆍ김 아

배경 목 : 본 연구는 실제 임상에서 류마티스 문의가 항 TNF 길항제가 응이 된다고 단하는 류마티스 염

환자들의 임상 양상을 알아보고, 이와 국내 항 TNF 길항제의 보험 기 을 비교하고자 하 다.

상 방법: 환자는 학병원 류마티스 내과을 방문하여 정규 으로 DAS28을 측정하는 류마티스 염 환자들 선정

하 다. 2가지 이상의 항류마티스약제(DMARD)를 3개월 이상 사용한 환자 류마티스 문의가 단하기에 TNF-길항제

가 응이 되는 환자를 선정하 다. 문의가 TNF-길항제가 필요하다고 단한 시 에서 환자의 기본 인구역학 특성과

DAS28, 발목 족지 포함한 총 40개 의 압통, 종창을 측정하고 성 반응 단백지표 (ESR, CRP)를

측정하 다. 수부, 족부 -후방 단순 촬 에서 modified Sharp-van der Heijde scoring 을 실시하여 방사선 소견을 정량하

다.

결과: 4곳의 학병원에서 류마티스 내과 문의 5명이 2010년 8월-2013년 1월까지 내원한 환자 총 117명의 환자에서

항 TNF 길항제가 응이 된다고 단하 다. 평균나이는 56세, 평균 치료 기간은 18.1±20.9개월이 다. 항 TNF 길항제

사용이 필요하다고 단되는 시 의 평균 DAS28는 4.64 (range, 1.19∼7.35)이 고, 28개 평균 부종 수는

4.1개(range, 0∼22), 압통 수는 8.7개 고(range, 0–28), 평균 ESR 값은 38.89 mm/hr (range 2∼140), 평균 CRP값은

1.7 mg/dL (range 0.1∼18.3) 다. 상 환자들의 modified Sharp van der Heijde score는 total score 36.7 (range 11∼56), erosion

score 12.1 (range 0∼20), narrowing score 24.5 (range 9∼39) 다. 이 생물학 제제를 사용을 실제로 시작한 환자는 80명

(68.4%) 이 다. 각 환자들의 국내 보험 기 만족 비율을 살펴보면 염증수치 기 을 만족하는 경우는 70명(59.8%), 활성

수 기 을 만족하는 경우는 19명(16.2%) 다.

결론: 류마티스 문의가 항 TNF 길항제 사용이 필요하다고 단하는 류마티스 염 환자들은 다양한 질병 활성도와

임상 양상을 보이고 있었다. 다수의 환자에서 보험 여 기 을 만족하지 못한 소견을 보인 만큼 합리 인 보험 여 기

의 검토가 이루어져야 할 것이다.

Journal of Rheumatic DiseasesVo l . 2 0 , Sup p l . 1 , May , 20 13 SLE-Clinical Aspects

S99

Hydroxychloroquine 망막병증의 선별검사 결과

성균 학교 의과 학 삼성서울병원 안과1, 성균 학교 의과 학 삼성서울병원 류마티스내과2

김상진1ㆍ황지원2ㆍ이민규1ㆍ이재 2ㆍ차훈석2ㆍ고은미2

배경 목 : Hydroxychloroquine은 비가역 망막 손상 그로 인한 심각한 시야 결손 시력 하를 유발할 수 있다.

본 연구는 hydroxychloroquine 망막병증의 발생 여부를 확인하고자 미국안과학회의 2011년 개정된 선별검사 권고안에

따라 선별검사를 시행하여 그 결과를 분석하고자 하 다.

상 방법: 류마티스내과에서 hydroxychloroquine을 복용했거나 복용 인 환자로 2011년 8월부터 2012년 12월까지

hydroxychloroquine 망막병증의 선별검사를 해 안과에 의뢰하여 안 검사 험 리 자동시야검사, 안 자가형 촬 ,

스펙트럼 역 빛간섭단층촬 을 시행한 환자의 의무기록을 후향 으로 분석하 다.

결과: Hydroxychloroquine을 복용했거나 복용 인 141명의 나이는 평균 44.7±12.9세 으며, 남자 12명(8.5%), 여자 129명

(91.5%)이었다. 유병된 질환은 신성 홍반성 루푸스 106명(75.2%), 류마티스 염 16명(11.3%), 쇼그 증후군 15명

(10.6%) 등이었다. Hydroxychloroquine의 평균 복용 기간은 69.0±39.5개월이었고 평균 복용량은 642.0±410.0 g이었다.

복용량 1,000 g 과인 환자는 27명이고, 5년 과 복용 환자는 65명이었다. Hydroxychloroquine 망막병증이 강하게

의심되는 환자는 2명(5년 과 복용자 3.1%)이었으며, 이 두 명은 모두 자각 증상이 없었고 각각 14.5년간 2088g, 9.9년

간 636g의 hydroxychloroquine을 복용하 다. 그 외의 안 이상 소견으로 망막신경섬유층결손, 망막 염, 망막색소상피

박리 등이 찰되었다. 망막신경섬유층결손은 hydroxychloroquine 5년 이하 복용군(69명 2명; 2.9%)에 비해 5년 과

복용군(72명 7명; 9.7%)에서 높게 나타났으나 통계 으로 유의한 차이는 없었다.

결론: Hydroxychloroquine 망막병증은 장기 복용 환자에서 이 에 외국에 보고된 것과유사한 빈도로 발생하 다. 빛간섭

단층촬 과 같은 검사 장비를 이용해 망막 이상을 조기에 발견할 수 있기 때문에 시력 하 등의 증상이 발생하기 에

Hydroxychloroquine 복용 환자를 상으로 선별검사를 시행하는 것이 필요하다.


S100

Comparison of Mycophenolate Mofetil and Intravenous Cyclophosphamide as Induction Therapy in Korean Patients with Lupus Nephritis

남 학교 의과 학 류마티스내과학교실1, 병리학교실2

Dong-Jin Park1, Ji-Hyoun Kang1, Kyung-Eun Lee1, Jeong-Won Lee1, Lihui Wen1, Tae-Jong Kim

1, Yong-Wook Park

1, Ji Shin Lee

2, Yoo Duk Choi

2, Shin-Seok Lee

1

Objectives: Although intravenous cyclophosphamide (IVC) pulses are generally accepted as standard therapy for induction treat-

ment of active proliferative LN, several clinical trials have suggested that MMF is at least as effective as IVC. MMF seems

to be consistently effective in all racial/ethnic groups compared to IVC which is shown as less effective in patients of African

or Hispanic descent. Nevertheless, it is necessary to compare these two treatment modalities among different racial or ethnic

groups, particularly in Asia. This study compared the efficacy of MMF and IVC as induction treatment for LN in ethnically

homogeneous Korean patients.

Methods: This study enrolled 49 LN patients with available kidney biopsy specimens. Sociodemographic, clinical, laboratory,

and treatment-related data at the time of kidney biopsy and during follow-up were obtained by reviewing the patients’ charts.

The renal biopsy specimens were reclassified according to the ISN-RPS classification, by 2 renal pathologists blinded to the

previous classification. The renal outcome was defined according to the ACR 2006 response criteria in clinical trials.

Results: Of the 49 patients, 28 (57.1%) were treated with IVC and 21 (42.9%) with MMF, both in combination with

prednisolone. The baseline characteristics of the two groups were comparable, except that the IVC-treated patients had lower

platelet counts, lower C3 levels, and higher activity scores in the renal biopsy compared to the MMF-treated patients. CR was

seen in 9 of 21 patients receiving MMF and 14 of 28 patients receiving IVC after 6 months treatment and in 11 of 21 patients

in the MMF group and 13 of 28 patients in the IVC group at 1 year. The number of patients achieving PR and NR did not

differ significantly at 6 and 12 months between the treatment groups.

Conclusion: These findings suggest that the efficacy of oral MMF at 1 year does not differ from that of IVC in induction

treatment of LN in ethnically homogeneous Korean patients. MMF may be considered first-line induction therapy for treating

LN in these patients.


S101

Persistent Dyslipidemia is a Risk Factor of Progression to Chronic Kidney Disease in Patients with Lupus Nephritis



1, Yong-Wook Park

1, Ji Shin Lee

2, Yoo Duk Choi

2, Shin-Seok Lee

1

Objective: To investigate the effect of dyslipidemia at baseline and during follow-up period on the progression to chronic kidney

disease (CKD) in patients with biopsy-proven lupus nephritis (LN).

Methods: We studied 68 patients who had kidney biopsy prior to the start of induction treatment, and who subsequently were

treated with immunosuppressive drugs for at least 6 months. Sociodemographic, clinical, laboratory including lipid profile, and

treatment-related data at the time of kidney biopsy and during follow-up were obtained by reviewing patients’ charts. In addition,

lipid profile data were collected at 6 months and 1 year of follow-up periods. Patients were divided into two groups based on

mean levels of LDL cholesterol: the ≥100 mg/dL group with 25 patients and the ＜100 mg/dL group with 43 patients. Cox-

proportional regression analyses were performed to identify independent predictors of progression to CKD in these patients.

Results: The higher LDL cholesterol group had a significantly older age at onset of LN, had higher WBC counts, and excreted

more 24-hour urine protein than the lower LDL cholesterol group (p=0.010, p=0.035, and p=0.048, respectively). The high LDL

cholesterol levels during the follow-up period was a significant predictor of CKD in LN patients in unadjusted model (hazard

ratio [HR] 3.997, 95% CI 1.193∼13.388, p=0.025), and this association remained significant after adjustment for confounders

including estimated glomerular filtration rate (HR 3.592, 95% CI 1.067∼12.094, p=0.039).

Conclusion: Our findings suggested that persistent dyslipidemia during 1-year follow-up after the onset of LN was an in-

dependent risk factor to predict the development of CKD in LN patients. Therefore, lipid profile should be monitored regularly

and dyslipidemia should be managed aggressively to prevent deterioration of kidney function in these patients.


S102

The Assessment of Psychological Stress Using Saliva in SLE

Department of Rheumatology, Ajou University School of Medicine, Korea

Ju-Yang Jung, Chang-Bum Bae, Jin-Young Nam, Hyoun-Ah Kim, Chang-Hee Suh

Stress has been known as a triggering factor in systemic lupus erythematosus (SLE). Saliva has several advantages as a source

of biological fluid to assess stress because it is less intrusive and easier to collect than blood. We investigated stress hormones,

disease biomarkers in saliva, and collected the questionnaire representing psychological distress in patients with SLE and normal

controls. Saliva were acquired from patients with SLE (n=110) and age, sex-matched healthy control (n=59). Salivary cortisol,

α-amylase, and IL-1β were measured by ELISA. Also, all participants filled out perceived stress scale (PSS), and Beck depres-

sion index (BDI) to quantify their stress and depression. The mean level of salivary α-amylase was higher in SLE than that

in NC (128.09±60.61 vs 101.56±54.30, p=0.004), however levels of cortisol and IL-1β were not different between SLE and

NC (p=0.79 and p=0.162, respectively). Salivary α-amylase was correlated with ESR, and IL-1β. Salivary IL-1β was correlated

with BDI, α-amylase, disease duration, and ESR in patients with SLE. The BDI was more increased in SLE than that in NC

(10.86±9.25 vs 5.37±4.82, p＜0.001). Though PSS had no difference, it was significantly correlated with change of SLEDAI

for 3 months (r2=0.262, p=0.006) in SLE. Salivary α-amylase was elevated in patients with SLE, though it wasn’t related with

disease activity. The patients with SLE were suggested be more depressed than normal healthy control. There was no difference

in recognizing stress, however, the activity of SLE became worse with increasing stress levels.

Journal of Rheumatic DiseasesVo l . 2 0 , Sup p l . 1 , May , 20 13 RA-Pathogenesis (III)

S103

Foxp3-Expressing Regulatory B Cells Inhibit Autoimmune Arthritis in a Mouse Model

The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Korea

Mi-Kyung Park, Young Ok Jung, Yu-Jung Heo, Eun-Kyung Kim, Hye-Jwa Oh, Young-Mee Moon, Sung-Hwan Park, Ho-Youn Kim, Mi-La Cho, Jun-Ki Min

Objective: The Foxp3 is a key regulator in the development and function of regulatory T cells (Tregs) and its expression was

thought to be T cell-resticted. The aim of this study was to investigate existence of Foxp3 expressing B cells and its function

in collagen-induced arthritis (CIA).

Methods: The protein and mRNA expression of Foxp3 in CD19+ B cells from mice was determined by flow cytometry, western

blotting and RT-PCR. A confocal microscope was used to visualize the location and expression of Foxp3 in B cells and T cells.

CD19+ B cells were transfected with shRNA or overexpressing vector for Foxp3. In vitro suppressive activity of Foxp3 expressing

B cells on T cell proliferation was assessed by 3H-thymidine incorporation assay. Foxp3-transfected B cells were adoptively

transferred to CIA mice. Therapeutic effects were evaluated by clinical symptoms and joint histopathology.

Results: We found that lipopolysaccharide (LPS) or anti-IgM stimulation induced Foxp3 expression in B cells. The

Foxp3-expressing B cells were found in spleen of mice. To generate Foxp3-expressing B cells in vitro, we have infected CD19+

B cells with a vector encoding the Foxp3. Transfection of Foxp3 conferred suppressive capacity on proliferation of responder

T cells cell-contact dependent. The shRNA for Foxp3 in B cells caused a profound defect in proliferation of responder T cells.

The adoptive transfer of Foxp3+CD19+ B cells effectively attenuated clinical symptoms of CIA with concomitant suppression

of IL-17 production and enhancement of Foxp3 expression in CD4+ T cells from splenocytes.

Conclusion: This finding indicates that Foxp3 is not solely restricted to T cells in the immune cells. The expression of Foxp3

in B cells is crucial for their immunoregulatory ability to limit autoimmunity.


S104

Treatment of Collagen-induced Arthritis Using Immune Modulatory Properties of Human Mesenchymal Stem Cells


박규형ㆍ문진희ㆍ강미일ㆍ이상원ㆍ이수곤ㆍ박용범

Objectives: Mesenchymal stem cells (MSCs) have immune modulatory properties. We investigated the potential therapeutic

effects of human bone marrow (BM)-, adipose tissue (AD)-, and cord blood (CB)-derived MSCs in an experimental animal model

of rheumatoid arthritis (RA), and explored the mechanism of MSC immune modulation.

Methods: We evaluated the therapeutic effect of clinically available human BM-, AD- and CB-derived MSCs in DBA/1 mice

with collagen-induced arthritis (CIA). CIA mice were injected intraperitoneally with three types of MSC. Treatment-control ani-

mals were injected with 35 mg/kg methotrexate (MTX) twice weekly. Clinical activity in CIA mice, degree of inflammation,

cytokine expression in the joint, serum cytokine levels, and regulatory T cells (Tregs) were evaluated.

Results: Mice treated with BM-, AD-, and CB-MSCs showed significant improvement in clinical joint score, comparable to

MTX-treated mice. Histologic examination showed greatly reduced joint inflammation and damage in MSC-treated mice compared

with untreated mice. Microcomputed tomography also showed little joint damage in the MSC-treated group. MSCs significantly

decreased serum interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, and interferon-γ and increased IL-10 and trans-

forming growth factor-β levels. Tregs were increased in mice treated with MSCs compared to untreated or MTX-treated mice.

Conclusion: Human BM-, AD-, and CB-MSCs significantly suppressed joint inflammation in CIA mice. The cells decreased

pro-inflammatory cytokines and upregulated anti-inflammatory cytokines and induced Tregs. Therefore, our study suggests that

the use of human BM-, AD-, and CB-MSCs could be an effective therapeutic approach for RA.


S105

Regulation of Apoptosis and Inflammatory Responses by IGFBP-3 in Fibroblast-like Synoviocytes and Experimental Animal Models

of Rheumatoid Arthritis

Department of Biochemistry, Chonbuk National University Medical School MD-PhD Student1, Jeonju Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of

Medicine2, Jinju, Korea

Hwa-Suk Lee1, Seong Ji Woo1, Sun-O Ka1, Hye Song Lim2, Hyun-Ok Kim

2, Byung-Hyun Park

1, Sang-Il Lee

2

Objective: Insulin-like growth factor binding protein-3 (IGFBP-3) is known to interfere with NF-κB signaling pathway and

effectively promotes the apoptosis in tumor cells by a variety of mechanisms. Based on the pivotal roles of NF-κB activation

and apoptosis resistance of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA), we postulated that IGFBP-3 could

have anti-arthritic effects.

Methods: To deliver IGFBP-3, we used an adenovirus containing IGFBP-3 cDNA (Ad-IGFBP-3) or IGFBP-3 mutant devoid

of IGF binding affinity but retains IGFBP-3 receptor binding ability (Ad-mtIGFBP-3). The regulatory roles of IGFBP-3 against

inflammation and bone destruction were defined in mice with collagen-induced arthritis (CIA).

Results: IGFBP-3 levels were significantly higher in patients with RA as compared with those with OA; this was notable in

patients with active RA. Ad-IGFBP-3 suppressed NF-κB activation, chemokine production, and matrix metalloproteinase secretion

induced by tumor necrosis factor-α (TNF-α) in RA-FLS. Ad-IGFBP-3 sensitized TNF-α-induced apoptosis of RA-FLS in vitro

and also significantly increased apoptosis in an in vivo model of Matrigel implants engrafted into immunodeficient mice.

Ad-IGFBP-3-injected CIA mice had an attenuated arthritis severity and reduced radiological and pathological abnormalities.

Moreover, Ad-IGFBP-3 down-regulated local and systemic levels of NF-κB-targeted proinflammatory cytokines. Of note,

RA-FLS and CIA mice treated with Ad-mtIGFBP-3 exhibited similar effects as Ad-IGFBP3 did.

Conclusion: Our results suggest that both inflammatory response and bone destruction are reduced with the blockage of NF-κB

activation and induction of apoptosis in RA-FLS by IGFBP-3. Therefore, IGFBP-3 may have a new therapeutic potential for

the treatment of RA.

Disclosure: This work was supported by a grant from the National Research Foundation of Korea funded by the Korean govern-

ment (No. 2012-0009319).


S106

CD70 Expressing CD4 T Cells Produce IFN-γ and IL-17 in Rheumatoid Arthritis

서울 학교 의과 학 내과학교실1, Division of Rheumatology Cooper Medical School of Rowan University, New Jersey, USA2

박진균1ㆍ한 훈

2ㆍ박지아

1ㆍ우윤정

1ㆍ김소

1ㆍ이은

1ㆍ이은

1ㆍ송 욱

1

Objectives: To explore the phenotype and cytokine production of CD70+ CD4 T cells in rheumatoid arthritis (RA).

Methods: Peripheral blood mononuclear cells (PBMCs) from 33 RA patients were isolated and frequencies of CD70+ cells

within different CD4 T subsets were analyzed using flow cytometry. Interferon (IFN)-γ and interleukin (IL)-17 production was

compared between the CD70+ and CD70- cells. Expression of master transcription factors T-bet, GATA3 and RORγT were

examined by real-time PCR. Results were expressed in mean±standard error of the mean.

Results: CD70+ cells were present within all T cell subsets, i.e. CD45RA+ CCR7+ naïve, CD45RA-CCR7+ central memory,

CD45RA-CCR7- effector memory, and CD45RA+ CCR7- terminally differentiated effector memory T cells with a frequency

of 4.4±1.2%, 3.9±0.45%, 4.1±0.7%, and 9.1±4.2%, respectively. As compared to CD70- cells, CD70+ CD4 T cells produced

significantly more IFN-γ and IL-17 after short activation. Resting CD70+ CD4 T cells preferentially expressed transcription

factor RORγT.

Conclusions: CD70+ CD4 T cells may directly contribute to RA pathogenesis by rapidly producing IFN-γ and IL-17. Targeting

CD70+ CD4 T cells might offer new therapeutic opportunities in RA.

Journal of Rheumatic DiseasesVo l . 2 0 , Sup p l . 1 , May , 20 13 Myositis and AOSD

S107

The Potential Role of Mast Cells in the C-Protein Induced Myositis Model


신기철ㆍ김은 ㆍ최지용ㆍ장성혜ㆍ송 욱

Background: Mast cells (MCs) function as immune sentinel cells in the tissue. The well-known cellular infiltrate in inflammatory

myositis mainly consists of macrophages and lymphocytes that produce numerous inflammatory cytokines and chemokines aug-

menting inflammatory cell infiltration and damage of myofibers. The role of tissue-resident MCs has not been well studied in

inflammatory myositis.

Objectives: To study the phenotype and role of MCs in a murine myositis model.

Methods: C-protein induced myositis (CIM) was induced with human skeletal C-protein fragment in 8 week-old female MC-defi-

cient SASH mice and C57BL/6 controls. Quadriceps muscles of both legs were harvested at day 21. Toluidine blue stain was

used to identify degranulating MCs in the muscle tissue. Immunohistochemistry was performed to detect mouse mast cell protease

(mMCP)-1, -4, -5, -6 positive MCs.

Results: MCs were mainly located in the connective tissue between fascicles showing a connective tissue MC phenotype. The

density of MCs and percentage of degranulating MCs per 5 high power field (HPF) were increased in CIM tissues. MC deficient

mice had lower histology score of muscle inflammation compared with controls. The difference mainly attributed to abrogated

invasiveness of inflammatory infiltrates into fascicles in MC deficient mice.

Conclusions: Connective tissue-type MCs in skeletal muscles are activated upon CIM induction. MCs facilitate tissue invasion

of inflammatory infiltrates into muscles in the CIM model.


S108

The Effect of CXCL10 Blockade in C Protein-induced Myositis

Chungnam National University Hospital1, Seoul National University College of Medicine2, Seoul, Niigata University Graduate School of Medical and Dental Sciences3, Niigata,

Tokyo Medical and Dental University4, Tokyo, Japan

Jinhyun Kim1, Jiyong Choi

1, Sung-Hye Park

2, Seung Hee Yang

1, Ji Ah Park

1, Kichul Shin

1,

Eun Young Lee1, Eun Bong Lee1, Hiroshi Kawachi3, Hitoshi Kohsaka4, Yeong Wook Song1

Backgrounds: CXCL10 (also called interferon-γ-inducible protein 10 [IP-10]) is a chemokine that plays a critical role in the

infiltration of T cell in autoimmune disease such as RA and SLE. CXCL10 is reported to be expressed in muscle tissue of

polymyositis. We investigated the role of CXCL10 and the effect of CXCL10 blockade in C protein-induced myositis, an animal

model of polymyositis.

Methods: C protein-induced myositis model was induced with human skeletal C protein fragment in 8-week-old female C57BL/6

mice. Immunohistochemistry was performed to detect CXCL10 and CXCR3, its receptor in muscle tissue. CXCR3 in mouse

splenocyte was investigated by flow cytometry. Migration assay of mouse splenocyte was performed with 5 μm pore transwell

system. Mice with C protein-induced myositis were treated with anti-CXCL10 antibody or control IgG 8 days after the induction

of myositis and the inflammation in muscle tissue was assessed 3 week after the induction.

Results: Immunohistochemistry showed the expression of CXCL10 and CXCR3 in the muscle of C protein-induced myositis.

Flow cytometry demonstrated increased CXCR3+CD4+ T cells (normal mice, 14.14%±1.09% vs. C protein-induced myositis,

37.50%±5.63%) and CXCR3+CD8+ T cells (normal mice, 35.55±2.41% vs. C protein-induced myositis, 79.00%±0.89%) in C

protein-induced myositis. Moreover, it was showed that IFN-γ+ cells were increased among CXCR3+CD8+ T cells compared

to CXCR3-CD8+ T cells (CXCR3+CD8+ T cell, 28.0 ± 4.2% vs. CXCR3-CD8+ T cell, 9.5 ± 1.5%, p = 0.016). Migration

of splenocyte was increased in response to CXCL10 (chemotactic index=1.91±0.45). Treatment with anti-CXCL10 antibody (n=10)

showed less inflammation score in muscles than treatment with control IgG (n=10; median [range], anti IP-10, 0.75 [0.25-2.00]

vs. control IgG, 1.43 [1.125-4.25], p=0.045).

Conclusion: CXCL10 was expressed in the inflammation of C protein-induced myositis model and its blockade suppressed

inflammation in muscle.


S109

Delta Neutrophil Index as an Early Marker for Differential Diagnosis of Adult-onset Still’s Disease and Sepsis


박희진ㆍ하유정ㆍ표정윤ㆍ박용범ㆍ이수곤ㆍ이상원

Objectives: To investigate the clinical implications of delta neutrophil index (DNI) to discriminate Adult onset Still`s disease

(AOSD) from sepsis.

Methods: We investigated the medical records of 13 patients with AOSD and 33 sex and age-matched patients with sepsis.

DNI and other laboratory values were assessed two or three times during the first 3 days and represented by their mean levels.

In all subjects, microbial tests were performed to exclude or confirm sepsis.

Results: The mean age of AOSD patients was 43.9 ± 13.4 years old and that of sepsis patients was 48.8 ± 11.0 years old.

There were no significant differences in white blood cell counts, neutrophil proportion, erythrocyte sedimentation rate (ESR)

and C-reactive protein (CRP) between two groups. AOSD patients had notably lower DNI than sepsis patients regardless of

the presence of bacteremia or not. However, both DNI and ferritin were not significant independent factors for sepsis in the

multivariate logistic regression analysis. Meanwhile, the AUROC of DNI was slightly higher than that of ferritin. When we set

DNI of 2.75% as the cut-off value for differential diagnosis of the two diseases, eleven (84.6%) of AOSD patients had a DNI

value below 2.75% and 2 (15.4%) of them had a DNI over 2.75%. In contrast, in sepsis patients only 1 (3.0%) had a DNI

below 2.75%. And the relative risk for predicting sepsis was 176.

Conclusion: We suggest that DNI may be a useful marker for the differential diagnosis of AOSD from sepsis in the early phase.


S110

Biomarkers as Reflecting Disease Activity in Korean Patients with Adult Onset Still’s Disease

Division of Rheumatology, Department of Internal Medicine, The Hospital for Rheumatic Disease, Hanyang University School of Medicine1, Institute of Rheumatology, Hanyang University2

Jin-Ju Kim1, Jae-Kong Kim

2, Dae-Hyun Yoo

1

Background: Adult onset Still’s disease (AOSD) is a rare inflammatory disorder of unknown etiology. Clinical manifestations

and laboratory findings are not disease-specific. Although various cytokines have been reported that they play important roles

in pathogenesis of AOSD, the utility of serum cytokines in clinical medicine is still controversial. The aim of this study is the

investigation of serum cytokines as biomarkers for reflecting disease activity among AOSD patients.

Methods: Total 34 patients who had available samples of both active and inactive states were enrolled. Twenty-six healthy

volunteers were enrolled as controls. Clinical and laboratory findings were collected in both disease states. Serum IL-18, IL-1β,

IL-6, MIF, TNF-α and IFN-γ were analyzed.

Results: Demographic features were similar between both groups. Serum IL-18, IL-1β, IL-6 and MIF were significantly in-

creased in active state compared with inactive state and controls. However, serum TNF-α and INF-γ were not well detected

in both groups and serum IL-1β was rarely detected in inactive state of AOSD. 82.4%, 73.5% and 50.0% of patients had increased

serum levels of IL-18, IL-6 and MIF during inactive state, they showed increased disease activity within seven months in 42.9%,

56.0% and 64.7% even though serum ESR, CRP and ferritin were normal. 17.6%, 50.0% and 29.4% of patients had increased

level of any one cytokine, any 2 cytokines and all 3 cytokines. Among them, each 33.3%, 26.7% and 90% of patients increased

disease activity after inactive state within several months. Patients with simultaneously elevated level of all 3 cytokines such

as IL-18, IL-6 and MIF in inactive state had risk of worsening clinical activity soon.

Conclusions: Serum cytokine such as IL-18, IL-6 and MIF can be used as markers to monitor disease activity in inactive

state. It may be considered for applying serum cytokine as a reference of remnant disease activity in each patient at the decision

of treatment intensity.

Journal of Rheumatic DiseasesVo l . 2 0 , Sup p l . 1 , May , 20 13 Epidemiology

S111

Prevalence of and Risk Factors for Spine OA and Its Association with Low Back Pain Among Community Residents in Korea

Department of Internal Medicine, Hallym University Sacred Heart Hospital1, Department in Preventive Medicine, Ajou University School of Medicine2, Korea

Sung Yeon Lee1, Young Ok Jung

1, Hyun Ah Kim

2, Seung Hun Lim

1, Nam Han Cho

1

Objectives: Low back pain (LBP) is an important public health problem of elderly people in industrialized societies. Although

lumbar spondylosis is considered a major cause of LBP and disability, the epidemiological study of lumbar spondylosis (spine

OA) in Asia has been scarcely reported. We investigated the prevalence of and the relevant risk factors for spine OA among

middle-aged and elderly rural community residents in Korea. We also explored the association of the radiographic lumbar spondy-

losis with LBP.

Methods: From Korean Health and Genome Study, 1795 subjects with LBP aged 40-79 years (58.7% were females) living

in a rural farming community (Anseong) in Korea were analysed. Demographic information was collected by an interview. The

point prevalence of LBP was obtained using a direct question and disability was measured by validated Korean version of the

Oswestry disability index (ODI). In lumbar spine radiographs, vertebral level from L1/2 to L4/5 were evaluated by Kellgren

–Lawrence (K-L) grading.

Results: Sixty-four percent of subjects had spine OA defied as K-L grade ≥2 spondylosis (74% among men, 58.4% among

women) and LBP was present in 34% of subjects (25.2% among men and 40.6% among women). Spine OA was more common

among men, although the prevalence of LBP was higher among women. Spine OA was weakly but significantly correlated with

Oswestery back pain index after adjustment of age and sex. The association between spine OA and LBP was observed only

among women. Age, manual work and history of hand or knee arthritis were risk factors for spine OA. Additionally, hypertension

and obesity were associated with spine OA defined as K-L grade ≥3.

Conclusions: This study among Korean rural community residents shows that the prevalence of spine OA was 64%. The associa-

tion between spine OA and LBP was observed only among women and spine OA was significantly correlated with the severity

of back pain.


S112

Prevalence and Incidence of Osteonecrosis in Patients with Systemic Lupus Erythematosus

Hanynag University Hospital for Rheumatic Disease, Korea

Young Bin Joo, Yoon-Kyoung Sung, Jee-Seon Shim, Jae-Hoon Kim, Hye-Soon Lee, Sang-Cheol Bae

Objectives: To estimate the prevalence and incidence of osteonecrosis in patients with systemic lupus erythematosus (SLE)

using the National Health Insurance (NHI) claims data.

Methods: This study was conducted with 25,358 SLE patients from the Korean NHI during 2006∼2010. AVN cases were

defined as at least ≥1 diagnosis of osteonecrosis [M870-3, M878-9, M905, M870x-3x M878x-9x, and M905x in the ICD-10].

The annual prevalence rates and annual incidence rateswere calculated by dividing the number of prevalent cases or incident

casesby SLE cases within that year. The robustness of definition of osteonecrosis was observed by sensitivity analysis of limiting

patients with special evidences (admission, going to the specialist, taking radiography). Comorbidities and prescribed medication

were compared between the patients with or without osteonecrosis.

Results: The annual prevalence of osteonecrosis (2006∼2010) were 31.5∼34.2 per 1,000, which are quite similar each year.

Incidence rates were 9.2 per 1,000 (95% CI 7.5∼10.9) in 2009 and 7.6 per 1,000 (95% CI 6.1∼9.1) in 2010. In sensitivity

analysis, prevalence and incidence in 2009 decreased to 28.9 per 1,000 (95% CI 25.9∼31.9) and 8.9 per 1,000 (95% CI 7.2∼

10.6), respectively. Prescribed medications of corticosteroid, immunosuppressant, antiplatelet agent, and lipid lowering agent were

more common in the patients with osteonecrosis than that without osteonecrosis, and the comorbidities of hypertension, dyslipide-

mia, renal involvement, and osteoporosis were also common in the patients with osteonecrosis than that without osteonecrosis.

Conclusion: This is the first report of prevalence and incidence of osteonecrosis in patients with SLE using large nationwide

survey. Our results may be possible to represent the entire SLE patients with osteonecrosis in Korea.

Disclosure: This study was supported in part by grants from the Korea Healthcare Technology R&D Project, Ministry of Health

and Welfare, Republic of Korea (A080588 and A120404).


S113

Prevalence and Incidence of Systemic Lupus Erythematosus in South Korea

Hanyang University Hospital for Rheumatic Diseases1, Clinical Research Center for Rheumatoid Arthritis (CRCRA)2, Korea University Kuro Hospital3, Seoul, Hanyang University Guri Hospital4, Guri, Korea

Jee-Seon Shim1,2

, Yoon-Kyoung Sung1,2

, Jae-Hoon Kim3, Hye-Soon Lee

4, Sang-Cheol Bae

1,2

Objective: Our aim was to estimate the nationwide prevalence and incidence of systemic lupus erythematosus (SLE) in South

Korea.

Methods: We used the National Health Insurance claims data covering almost all Korean (∼50 million) from 2006 to 2010.

Individuals with SLE were identified if they have 1) experienced at least one hospitalization for SLE (ICD-10 code: M32), or

2) taken at least one concomitant prescription of immunosuppressant and hydroxychloroquine, or 3) had anti-dsDNA antibody

test (≥2) or complement test (≥2) during each calendar year. Incident cases were defined only if they hadn’t been SLE prevalent

for the preceding two years and were SLE prevalent for two years in a row after that.

Results: Annual prevalence (per 100,000) tended to slightly increase from 20.6 (95% CI, 20.2∼21.0) in 2006 to 26.5 (95%

CI, 26.0∼27.0) in 2010, and the incidence (per 100,000) ranged 2.5 (95% CI, 2.4∼2.6) in 2008 to 2.8 (95% CI, 2.7∼2.9)

in 2009. SLE prevalent patients were ∼6-fold more in females and the female-to-male ratio of incidence was ∼9. Both of

the prevalence and incidence significantly increased with increasing age and then significantly decreased after its peak at the

age of 30-39 years. This tendency, however, wasn’t obvious in males.

Conclusion: The nationwide prevalence (per 100,000) of SLE in Korea was 20.6 in 2006 to 26.5 in 2010 and the incidence

(per 100,000) was about 2.5.

(2010. 1. 1∼2010. 12. 31)


[활막염연구회]

Special Lectures I


S117

Intracellular Heparin Alleviates T Cell-mediated Inflammatory Arthritis by Inhibiting RhoA-dependent Transcellular Diapedesis

Division of Rheumatology, Department of Internal Medicine, Department of Biochemistry and Cellular Biology, and Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, Korea

Young Mo Kang

Heparin may alleviate chronic inflammatory arthritis. However, the anti-inflammatory effects of heparin have not been clarified,

and the anticoagulant activity and poor oral bioavailability of heparin limit its use as an anti-inflammatory agent. Conjugation

of bis-deoxycholic acid to 6-O-desulfated low molecular weight heparin (6DSHbD) abrogated anticoagulant activity. Moreover,

6DSHbD was efficiently internalized by activated endothelial cells via a 2-step model, in which heparin attaches to adhesion

molecules that facilitate accessibility of the bile acid conjugate to membrane transporters. The critical role of P-selectin during

endothelial cell uptake of 6DSHbD by arthritic tissue was confirmed in p-selectin-/- arthritic mice. Intracellular 6DSHbD inhibited

transcellular diapedesis of T cells through activated endothelial cells and impaired both the formation of ICAM-1-rich docking

structures at the T cell contact surface and subsequent cytoskeletal rearrangement. Furthermore, 6DSHbD blocked activation of

RhoA GTPase and phosphorylation of ezirin/radixin/moiesin, thereby impairing lymphocyte transcellular transmigration.

Administration of 6DSHbD revealed good oral bioavailability and preferential delivery to inflamed joint tissue, which inhibited

effector T cell homing to arthritic joints. Aggravation of collagen-induced arthritis conferred by the transfer of effector T cells

was suppressed by oral 6DSHbD. Thus, 6DSHbD exerts anti-inflammatory effects and may have applications in the treatment

of chronic inflammatory arthritis.


S118

Autophagy: An Innate Immune Effector Against Mycobacteria

Department of Microbiology and Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon, Korea

Eun-Kyeong Jo

Human tuberculosis remains a major public health problem worldwide. In developing countries, tuberculosis is highly endemic,

and its incidence is increasing as a consequence of the human immunodeficiency virus co-infection. Mycobacterium tuberculosis

(Mtb) is a highly successful pathogen that enhances its own intracellular survival by arresting phagolysosomal fusion. Recently,

autophagy has emerged as a crucial defence strategy against intracellular Mtb infection, through stimulation of the fusion of

phagosomes and lysosomes. Last several years, my group has focused on investigation of the roles of antibacterial autophagy

and innate immunity against mycobacteria. Another major goal of our research is to investigate the mechanisms by which autoph-

agy activates innate immunity against mycobacterial infection. In our previous studies, we found that vitamin D-dependent host

innate immune responses against mycobacteria are mediated through autophagy activation and cathelicidin expression. Human

cathelicidin was important for direct antimicrobial responses and also in mediating antibacterial autophagy. We also reported

that antibiotic-induced autophagy activation is essentially involved in the host defence and antimicrobial responses during myco-

bacterial infection. Bacterial and cellular reactive oxygen species were required for antibiotic-induced autophagy activation during

mycobacterial infection. These findings underscore the importance of host autophagy in successful antimicrobial responses against

mycobacteria. Currently, we are searching for autophagy-activating agents in macrophages infected with Mtb. In this talk, our

recent findings about a novel role of AMP-activated protein kinase-activating agents will be also discussed in promoting host

innate defense against intracellular bacteria through autophagy pathway.


S119

Mycobacterium Tuberculosis Heparin-binding Hemagglutinin and HspX, A Novel TLR4 Agonist, Induces Dendritic Cells-based Immunotherapy

Via Drives Th1 Immune Response

Department of Immunology, Lab of Dendritic Cell Differentiation & Regulation, School of Medicine, Konkuk University, Chungju, Korea

In Duk Jung, Hyun Kyu Kang, Yeong-Min Park

An immunoadjuvant being capable of inducing properly dendritic cells (DC) maturation to enhance cellular immunity is a key

factor in DCs-based immunotherapy. Here, we investigated the therapeutic efficacy of Mycobacterium tuberculosis hemag-

glutinin-binding hemagglutinin (HBHA) and HspX, as an immunoadjuvant in DC-based tumor immunotherapy and its adjuvant

capacity in the activation of DC and cytotoxic T lymphocytes (CTLs), and also determined whether HspX regulated the Th1/Th2

immune response by using an ovalbumin-induced allergic asthma. In this study, we showed that HBHA and HspX recognizes

Toll-like receptor 4 (TLR4) and induces DC maturation, and pro-inflammatory cytokine production (TNF-α, IL-1β, and IL-6)

partially modulated by both MyD88 and TRIF pathways. The administration of HBHA-stimulated DCs (HBHA-DCs) and

HspX-DCs increased the activation of naïve T cells, effectively polarize CD4+ and CD8+ T cells to secrete IFN-γ, and enhanced

the cytotoxicity of splenocytes against HPV-16 E7 (E7) -expressing TC-1 murine tumor cells in therapeutic experimental animals.

Treg cells (CD4+CD25+Foxp3+ cells) were significantly reduced in both splenocytes and tumor tissues from mice administered

by HspX-DCs. In addition, HspX-DCs increased interferon-gamma, IL-17A, IL-12 and TGF-beta production and T-bet gene ex-

pression but reduced Il-13 production and GATA-3 gene expression in allergic asthma model. Administration of HspX-DCs also

inhibited asthmatic reactions as demonstrated by an increase in the number of eosinophils in bronchoalveolar lavage fluid, an

increase in inflammatory cell infiltration in lung tissues, airway luminal narrowing, and airway hyperresponsiveness. Moreover,

HspX-DCs also increase OVA-induced decrease of Treg cells in mediastinal lymp node. These findings suggest that HBHA and

HspX enhances the polarization of T effector cells toward a Th1 phenotype through DC maturation and plays a critical role

in DC-based immunotherapy in tumor-bearing mice, and amelioration the pathogenic process of asthmatic inflammation in mice.

Rheumatoid arthritis (RA) a systemic inflammatory disease resulting from an autoimmune response to self-antigens, leading

to inflammation of synovial tissue of joints and subsequent cartilage and bone erosion. Current disease-modifying anti-rheumatic

drugs and biologic inhibitors of TNF, IL-6, T cells and B cells block inflammation nonspecifically, which may lead to adverse

effects, including infection. The development of antigen-specific strategies in RA has so far been limited by insufficient knowledge

of autoantigens, of the autoimmune pathogenesis of RA and of the mechanisms of immune tolerance in man. Effective toler-

ance-inducing antigen-specific immunotherapeutic strategies hold promise of greater specificity, of lower toxicity and of a lon-

ger-term solution for controlling or even preventing RA.

Therefore, HBHA and HspX may be useful as an effective adjuvant for enhancing the therapeutic response of DC-based im-

munotherapy including tumor, asthma, and RA.

(2010. 1. 1∼2010. 12. 31)



Oral Presentation I


S123

Dysfunction of Natural Killer T Cells in Patients with Active Mycobacterium tuberculosis Infection

Department of Rheumatology, Chonnam National University Medical School and Hospital1,Department of Laboratory Medicine, Chonnam National University Medical School and Hospital2,

Department of Pulmonary and Critical Care Medicine, Chonnam National University Medical School and Hospital3

Young-Nan Cho1, Seung-Jung Kee2, Yong-Soo Kwon3, Sung-Ji Lee1, Hye-Mi Jin1, Mun-Ju Kim1, Jae-Yee Kim1, Hyun-Ju Jung1, Tae-Jong Kim1, Shin-Seok Lee1, Yong-Wook Park1

Natural killer T (NKT) cells are known to play a protective role in the immune responses of mice against a variety of infectious

pathogens. However, little is known about the detailed information of NKT cells in patients with Mycobacterium tuberculosis

(MTB) infection. The aims of this study were to examine NKT cell levels and functions in patients with active MTB infection,

to investigate relationships between NKT cell levels and clinical parameters, and to determine the mechanism responsible for

poor response to α-galactosylceramide (α-GalCer). NKT cell levels were significantly lower in the peripheral blood of pulmonary

tuberculosis and extra-pulmonary tuberculosis patients, and proliferative responses of NKT cells to α-GalCer were also lower

in patients, whereas NKT cell levels and responses were comparable in latent tuberculosis infection subjects and healthy controls.

Furthermore, this NKT cell deficiency was found to be correlated with serum C-reactive protein levels. In addition, poor response

to α-GalCer in MTB patients was found to be due to increased NKT cell apoptosis, reduced CD1d expression, and a defect

in NKT cells. Notably, MTB infection was associated with an elevated expression of the inhibitory programmed death (PD)-1

receptor on NKT cells, and blockade of PD-1 signaling enhanced the response to α-GalCer. This study shows that NKT cell

levels and functions are reduced in MTB patients, and these deficiencies were found to reflect the presence of active MTB.


S124

류마티스 염 환자의 액유래 간엽 기세포의 질환시기에 따른 분화 면역억제능의 차이

경상 학교 의학 문 학원 류마티스내과1, 경상 학교 수의과 학2

김 옥1ㆍ천윤홍1ㆍ하 술1ㆍ임혜송1ㆍ이원재2ㆍ이성림2ㆍ이상일1

배경 목

간엽 기 세포(Mesenchymal stem cell, MSC)는 osteocyte, adipocyte, chondrocyte 등으로 분화 할 수 있는 구 세포로

면역억제능력이 있어 류마티스 질환의 새로운 치료방법으로 다양하게 연구되고 있다. MSC는 골수, 지방세포, 활막,

액 등 다양한 조직으로부터 추출 배양된다. 그러나, 액, 특히 류마티스 염(Rheumatoid arthritis, RA) 환자의

액에서 추출한 MSC에 한 연구는 거의 없다. 우리는 RA환자의 액에서 추출한 MSC를 RA의 질환시기에 따라 분류

하고 그 특성을 분석하 다.

방 법

Early RA 6명, advanced RA 6명, 정상인 6명의 액을 채취하고 MSC를 배양하 다. 유세포 분류기를 사용하여 CD44,

CD90, CD105, vimentin, CD34, CD45 등 MSC의 surface markers의 발 을 확인하 다. Oil Red-O, von Kossa, alkaline phos-

phatase (ALP), Alizarin red 염색 q-PCR 을 이용한 조직특이 유 자 검증을 통해 분화능을 평가하 으며, 증식능력은

MTT방식으로 평가하 다. 백 구 혼합반응과 Collagen induced mice (CIA)를 통해서 면역억제능 염에 한 억제

효과를 평가하 다.

결 과

RA 환자는 모두 여성으로, early RA는 질병기간 3.58±3.15년, 나이 60.8±6.83세, DAS28 5.45±1.53 , Modified Sharp score

는 20.2±13.92 이었다. Advanced RA는 14.6±6.11년, 58.6±3.29세, DAS28 4.05±1.12 , Modified Sharp score는 61.6±15.68

이다. 건강 조군은 모두 남자로 나이는 23.0±1.22세이었다. 세 군에서 MSC의 surface marker의 차이는 찰되지 않았다.

Von Kossa, ALP, Alizarin red 염색과 qPCR검사를 통해서 early RA-MSC의 골분화 능력이 advanced RA나 정상인에 비해서

증가된 소견을 보 다. 지방조직으로의 분화 능력은 세군이 비슷하 다. MTT 검사에서 RA-MSC의 증식능력이 정상인에

비해 감소되었다. CIA 실험에서 PBS 투여군에 비해서 normal-MSC와 early RA-MSC 투여군에서 clinical score, ankle thick-

ness, 조직학 검사, micro-CT 등에서 염 억제효과가 찰되었다. 그러나, advanced RA-MSC는 CIA 모델에서 유의한

염 억제 효과를 보이지 않았다.

결 론

RA-MSC는 RA의 질환시기에 따라서 분화능 면역억제능의 차이을 나타내며, early RA-MSC는 정상인 MSC와 유사한

CIA 억제효과를 나타내었으나 advanced RA-MSC는 CIA 억제효과가 없었다. RA-MSC의 자가이식을 RA의 치료에 이용하

기 해서는 질환시기에 따른 RA-MSC의 특성 규명에 한 추가 인 연구가 더욱 요구된다.

(2010. 1. 1∼2010. 12. 31)


[활막염연구회]어떻게 실험을 시작할 것인가?

(활막염 연구회 홈페이지 활용 Tips)


S127

어떻게 실험을 시작할 것인가? (활막염연구회 홈페이지 활용 Tip)

원 학교 의과 학

이 명 수

(2010. 1. 1∼2010. 12. 31)



Special Lectures II


S131

Techniques in Human T Cell Study: Application for Rheumatology

KAIST 의과학 학원

신 의 철

Rheumatoid arthritis 등 류마티스내과 역에서 다루는 각종 질환의 병태생리에서 각종 면역세포들이 주요 역할을 하고

있다. 면역세포들 에서도 특히 T세포는 항원-특이 세포 면역반응을 담당하며, 도움(helper) 조 (regulatory)기능을

통하여 면역반응의 심 역할을 한다.

Rheumatoid arthritis 등의 면역학 병태생리 연구에 있어 지난 수십 년 간 마우스 모델을 활용함으로써 많은 발 이

있었으나, 최근에 마우스 모델과 실제 환자에서의 면역 염증 반응이 상이함이 알려 지면서 차 환자에서의 면역세포

를 직 분석하고 연구하려는 노력들이 행해지고 있다.

그러나 환자에서 항원-특이 T세포를 연구하는 데에는 많은 어려움이 있다. 마우스 연구의 경우 항원-특이 T세포 연구의

어려움을 T세포 수용체(T cell receptor) 형질도입(transgenic) 마우스를 이용하여 상당 부분 해결해 왔으나, 사람을 상으로

한 연구에서는 이러한 방법을 용할 수 없으므로 그 동안 많은 어려움이 있었다. 하지만 최근에 사람 T세포를 연구하는

각종 기법들이 개발되어 환자의 항원-특이 T세포를 in vitro 배양 없이 생체 외에서 바로(direct ex vivo) 분석할 수 있게

되었다.

본 강의에서는 사람 T세포를 연구하는 방법에 있어서 최근 발 을 소개하고 류마티스성 질환 연구에 이를 어떻게 용

할 수 있는지 소개하고자 한다. 특히 항원-특이 T세포 연구 기법을 주로 소개할 것이며, 환자에서의 항원-특이 T세포

연구의 주요 사례로서 최근 심을 받고 있는 citrullinated protein-특이 T세포의 연구 사례들을 살펴보고자 한다.


S132

Genetic Predispositions to Rheumatoid Arthritis and Lupus

Department of Biological Sciences, KAIST, Daejeon, Korea

Taehyeung Kim, Kwangwoo Kim, Tae-Un Han, Changsoo Paul Kang, Changwon Kang

Genetic studies of human autoimmune diseases of rheumatism such as rheumatoid arthritis (RA) and systemic lupus eryth-

ematosus (SLE) have identified many genetic risk factors for these diseases contributing to the function of the immune system,

and have generated testable hypotheses to explain disease pathogenesis, although they have made limited impact on clinical prac-

tice and drug discovery yet. Functional data are emerging for incorporating genetic polymorphisms into pathogenic mechanisms,

and epigenetic studies are emerging for translating environmental exposures into pathogenic phenotype. However, interplays be-

tween genetic and environmental factors and between genetic risk factors are poorly understood and need to be further investigated.

Here are presented several new discoveries of ours on epistatic (gene-gene) interactions on susceptibility to RA and/or SLE,

where the effects of two risk alleles were simply additive to each other with no interaction between them, or were not additive

with either redundant or synergistic interaction between them. New insights coming from these genetic interaction studies of

RA and SLE would help elucidate pathogenic mechanisms as well as develop innovative therapeutic targets for these complex

diseases.

(2010. 1. 1∼2010. 12. 31)



Oral Presentation II


S135

Leukocyte-Specific Protein 1 (LSP-1) Is A Negative Regulator of T Cell Migration

Research Institute of Immunobiology, Catholic Research Institute of Medical Science1, Department of Internal Medicine, Catholic University of Korea2, Seoul, Korea

Seong-Hye Hwang1, Nam-Hoon Kim1, Seung-Ah Yoo1, Chul-Soo Cho1,2, Wan-Uk Kim1,2

Rheumatoid arthritis (RA) is characterized by increased migration of activated T cells into the joints, which is triggered by

chemokines, including stromal cell-derived factor-1 (SDF-1). In this study, we investigated the role of leukocyte-specific protein

1 (LSP1), a strong regulator of neutrophil and macrophage migration, in the T cell migration and in the RA pathogenesis. We

found that LSP1 was expressed in the inside of CD4+ T cells, CD8+ T cells, and Jurkat T cells, as determined by flow cytometry

and Western blot analysis. Stimulation of T cells with anti-CD3 antibody (Ab) plus anti-CD28 Ab, PHA, TNF-α or PMA plus

ionomycin resulted in an increase in LSP1 expression. Over-expression of LSP1 in Jurkat T cells showed a lesser degree of

cell migration in response to SDF-1. In addition, pERK2 expression levels were also decreased in LSP1-overexpressed Jurkat

cells stimulated with SDF-1. On immunohistochemical staining, LSP1 was expressed in T cell zone of RA synoviums, but its

expression level in peripheral blood T cells was significantly decreased in RA patients than in healthy controls. Inducible ex-

pressions of LSP1 in peripheral T cells stimulated with PHA, TNF-α or PMA plus ionomycin were also markedly reduced

in RA patients than in healthy controls. Importantly, CD4+ T cells isolated from Lsp1-/- mice showed enhanced migratory capacity

to SDF-1 compared with wild-type. Moreover, in delayed-type hypersensitivity model of arthritis, Lsp1-/- mice developed ex-

aggerated arthritis. These results suggest that LSP1 regulates the migration of human T cells. The decreased expression of LSP1

in peripheral T cells may increase migration of the cells into the joints, involving RA pathogenesis.


S136

PH-responsive Nanoparticles Carrying Methotrexate for Treatment of Inflammatory Arthritis

Division of Rheumatology, Department of Internal Medicine, Kyungpook National University, School of Medicine1, Department of Biochemistry & Cell Biology, Kyungpook National University, School of Medicine2, Cell & Matrix

Research Institute3, Department of Polymer Science and Engineering, Sungkyunkwan University4, Korea

Shijin Sung1, Mahmudul Md Alam1,2, Jin Hee Kang1, Hasan Al Faruque1,2, Keum Hee Sa1,3, Jae Hyung Park4, Young Mo Kang1,2,3

Tissue targetability and site-specific release of drug using microenvironment sensing nanoparticles (NP) are critical factors for

effective treatment for chronic inflammatory arthritis. In the present study, we used a biodegradable polymer-based NP coupled

with pH-responsive mechanism to counter premature release and enhance targeted drug delivery in arthritis. We show that NP

labeled with Cy5.5 was effectively accumulated within macrophages compared with monocytes, but not within fibroblast-like

synoviocytes. Uptake of NP by macrophages was inhibited by wortmannin but not by nystatin, dynasore, amiloride, or rifampin.

Within the cytoplasm NP was colocalized with Rab5 at subcortical area, followed by co-localization with Lysotracker. NP was

accumulated within inflamed joint tissue as well as the liver. Treatment with methotrexate (MTX)-loaded NP suppressed the

clinical arthritis indices of collagen-induced arthritis (CIA), but the efficacy was similar to MTX without NP. The ratio of accumu-

lation within inflamed joint tissues versus the liver was substantially enhanced with pH-responsive NP compared to NP. Treatment

with a high dose of MTX (50 mg/kg twice a week) with pH-responsive NP was well tolerated while the same dose of MTX

resulted in lethality in CIA mice. The pH-responsive NP drug carrier offers a translatable approach that can be applied to diverse

targeted nanosystems and shows promising potential as a drug carrier for arthritis therapy.


S137

Oleanolic Acid Acetate Inhibits Osteoclast Differentiation by Downregulating PLCγ2-Ca2+-NFATc1 signaling, and Suppresses bone loss in mice

Division of Rheumatology, Department of Internal Medicine1, Department of Anatomy, School of Medicine, Wonkwang University2, Korea

Chang Hoon Lee1, Ju-Young Kim

2, Jaemin Oh

2, Myeung Su Lee

1

Owing to their potential pharmacological activities in human disease, natural plant-derived compounds have recently become

the focus of increased research interest. In this study, we first isolated oleanolic acid acetate (OAA), a triterpenoid compound,

from Vigna angularis (azuki bean) to discover anti-bone resorptive agents. Many studies have identified and described the various

medicinal effects of V. angularis extract, but the pharmacological effect of OAA-derived V. angularis extract, particularly the

effect on osteoclastogenesis, is not known. Therefore, we investigated the effect and mechanism of OAA in receptor activator

of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and bone resorption. OAA inhibited RANKL-induced

osteoclast differentiation in bone marrow macrophages (BMMs) without any evidence of cytotoxicity. Interestingly, OAA sig-

nificantly inhibited phospholipase Cγ2 (PLCγ2) phosphorylation, calcium ion (Ca2+)oscillation,and nuclear factor of activated

T cell c1 (NFATc1) expression in RANKL-stimulated BMMs, but did not affect RANKL-induced mitogen-activated protein

kinase. OAA also inhibited the bone-resorbing activity of mature osteoclasts. Furthermore, mice treated with OAA demonstrated

marked attenuation of lipopolysaccharide-induced bone erosion based on micro-computed tomography and histologic analysis of

femurs. Taken together, the results suggested that OAA inhibited RANKL-mediated osteoclastogenesis via PLCg2–Ca2+-NFATc1signaling in vitro and suppressed inflammatory bone loss in vivo.

Keywords: Osteoclast, Oleanolic acid acetate, PLCγ2, Calcium oscillation, NFATc1

(2010. 1. 1∼2010. 12. 31)


[류마티즘골대사연구회]


S141

Runx2 Stability and Transcriptional Activity is Regulated by Pin1

Department of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University

Hyun-Mo Ryoo

Pin1 is a member of the peptidyl prolyl cis-trans isomerase (PPIase) superfamily that catalyzes the isomerization of cis-trans

conformations of rigid peptide bonds in the proline backbone, thereby altering the structural conformation of the protein (Lu

et al., 2007; Lu and Zhou, 2007; Yeh and Means, 2007). Among PPIases, Pin1 is unique in that its association with substrates

involves a WW domain that preferentially recognizes sequence motifs containing a phosphoserine or a phospho-threonine followed

by a proline (pS/T-P motif, proline-directed phosphorylation) in target substrates. Pin1 frequently functions as a binary switch

in fate-determining pathways depending on the cis or trans conformation of the target protein and is tightly associated with cell

signaling and Ser/Thr kinase activity.

RUNX2 haploinsufficiency is the cause of cleidocranial dysplasia (CCD) (Mundlos et al., 1997). A recent mouse genetic study

indicated that Runx2 dosage is a critical determinant of the penetrance of the CCD phenotype (Lou et al., 2009). The genetic

insufficiency of Runx2 was overcome by osteoblast-specific overexpression of constitutively-active MEK1 (MEK1-Ca) and was

exaggerated by the expression of dominant-negative MEK (Ge et al., 2007). These results suggested that ERK/MAPK-induced

phosphorylation of Runx2 may stimulate its transcriptional activity, thereby masking the effects of the genetic insufficiency of

the Runx2 heterozygote. Pin1 target sequences are shared by several protein kinases, such as ERK, CDK and GSK3a (Hsu et

al., 2001; Monje et al., 2005; Munoz et al., 2007; Patra et al., 1999; Yeh et al., 2004; Zheng et al., 2009), indicating that

ERK-phosphorylated Runx2 could also be the target of Pin1-mediated conformational and functional alterations. We have shown

previously that FGF-signaling stimulates Runx2 phosphorylation and transcriptional activity (Kim et al., 2006; Kim et al., 2003)

in addition to RunX2 acetylation and ubiquitination (Lee et al., 2010).

We found in this study that Pin1 mutant mice developed CCD-like phenotypes with hypoplastic clavicles and open fontanels

found in the Runx2+/- mice. In addition, Pin1 interacts with the Runx2 C-terminus following a phosphorylation event.

Pin1-mediated proline isomerization stabilizes the Runx2 protein by enhancing its acetylation and stimulating its transactivation

activity. Thus, CCD-like bone phenotypes observed in the Pin1 mutant mice could be indirectly resulted from a decrease in

the Runx2 protein stability and transactivation activity caused by Pin1 deficiency. Hence, the structural modification of Runx2

by Pin1 could be a novel therapeutic target for osteogenesis.


S145

Oxidative Stress & Osteoporosis

가톨릭 학교 부천성모병원 류마티스내과

민 기

활성 산소종(reactive oxygen species, ROS)은 세포 사의 부산물로 주로 마이토콘드리아의 자 운반 과정에 의해서

발생되고 이외에 endoplasmic reticulum, nuclear membrane, plasma membrane, peroxisome과 같은 membrane-bound 세포내

기 과 련되어 있는 oxidase에 의해서도 만들어진다. 한 xanthine oxidase, aldehyde oxidase, dihydroorotate dehydrogen-

ease, flavoprotein dehydrogenase, tryptophan dioxygenase 등과 같은 가용성(soluble) 효소에 의해서도 ROS가 생성된다 (1).

산화스트 스(oxidative stress)는 hydrogen peroxide, hydroxyl radical, super oxide anion과 같은 활성 산소종의 양이 이를

제거하는 catalase, superoxide dismutase, glutathione reductase와 같은 항산화 효소 glutathione과 같은 항산화 물질보다

많은 경우를 말한다.

활성 산소종은 인체에 침입한 세균에 한 방어 역할을 담당하며 한 세포 내 신호 달자의 역활을 담담하고 있다.

그러나 과도한 산화 스트 스는 세포막, 지질, 핵산, 단백질, 로테오 라이칸(proteoglycan), 콜라겐(collagen) 등과 같은

세포외 기질에 손상을 수 있다. 이로 인해 노화, 류마티스 염, 골 염, 당뇨병, 죽상 경화, 암, 골다공증 등의

발병에 련한다고 알려져 있다 (2).

골다공증은 골량이 감소되고 골의 미세구조가 약화되어 골 이 일어나기 쉬운 상태를 특징으로 하는 질환이다. 는

재형성 과정이 꾸 히 일어나는 활동 인 조직으로 손상된 를 골 세포가 흡수, 제거하는 골 흡수 과정과 같은 자리에

조골세포에 의해 같은 양의 가 생성되는 골 형성과정이 순차 으로 일러난다. 골 세포의 활성도가 증가하거나 조골세

포의 활성도가 감소하게 되면 골다공증이 발생한다. 골다공증은 노화, 양 상태, 호르몬, 사이토카인과 같은 다양한 원인

에 의해 발생한다. 노화에 따른 골 감소는 산화 스트 스 내인성 당질 코르티코이드 증강에 의한 조골세포와 골세포의

세포 사멸사, 조골세포 형성(osteoblastogenesis) 감소에 기인하며 지질 산화에 의한 지방형성 증가로 조골세포 형성이 억제

되는 것도 련되어 있다 (3).

골세포 분화는 receptor activator of nuclear factor kappa-B ligand (RANKL)과 macrophage colony-stimulating factor (M-CSF)

의 작용에 의해 일어난다. RANKL이 수용체인 RANK와 결합하게 되면 activated T cells cytoplasmic-1 (NFATc1), nuclear

factor kappa B (NF-κB), phosphatidylinositol, 3-kinase (PI3K)/Akt, Jun N-terminal kinase (JNK), extracellular signal-regulated

kinase (Erk), p38 mitogen-activated protein kinase (MAPK)의 신호가 활성화 된다. 이러한 신호 달 과정에 TRAF 6, Rac

1, NADPH oxidase 1 (Nox 1) 등을 통해 활성 산소종이 생성되어 골세포 분화에 요한 역할을 담당한다 (1).

폐경 후 골다공증 환자의 청에서 산화 스트 스를 반 하는 8-OH-dG 농도가 골흡수 지표와 유의한 양 상 계를

보이고 골 도와는 음 상 계를 나타낸다는 보고가 있다 (4). 한편 폐경 후 골다공증 환자의 액에는 항산화 물질로

알려진 carotenoid, uric acid의 농도가 높을수록 골 도가 높고 vitamin C, vitamin E, vitamin A, uric acid와 같은 비효소성

항산화 물질과 superoxide dismutase, glutathione peroxidase와 같은 효소성 항산화 물질이 감소되어 있다는 보고가 있다

(5,6). 폐경 후 골다공증이 발생한 환자 장기간 비타민 C를 복용한 경우 복용하지 않은 환자 군에 비해 퇴 경부

골 도가 의미있게 증가한다는 보고가 있다 (7).

항산화 효과를 가지고 있는 Fisetin, 6,4'-dihydroxy-7-methoxyflavanone, Coenzyme Q10 (CoQ10), selenium, curcumin, a-lipoic

acid 등은 골세포 분화를 억제한다 (8-11).

산화 스트 스가 조골세포의 분화를 억제한다는 보고들이 있다. hydrogen peroxide는 구조골 세포주인 MC3T3-E1 세포

에 의한 무기질 침착(mineralization)을 억제한다 (12). 산화 스트 스는 ERK와 NF-kB 활성화를 통해 rabbit bone marrow

stromal cell과 calvarial osteoblast의 조골세포로의 분화를 억제하고 구조골세포에서 beta-catenin의 T cell factor를 통한

S146 민 기: Oxidative Stress & Osteoporosis

사가 Forkhead box O를 통한 사로 바 도록 하여 Wnt 신호 달 과정이 억제된다 (13,14). 그리고 산화 스트 스는

PKCβ/p66shc/NF-κB 신호 달 과정을 활성화 시켜 조골세포의 세포자멸사(apoptosis)를 유발한다 (15). 당질코르티코이드

와 종양괴사 인자 알 는 조골세포에서 산화 스트 스를 증가시켜 Wnt를 통한 신호 달을 억제한다 (16).

한편 항산화 물질이 산화스트 스에 의한 조골세포로의 분화 기능 억제 효과를 감소시킨다는 연구 결과들이 있다.

2,6-diisopropylphenol은 caspase-3를 억제하여 골세포의 세포자멸사를 억제하며 N-acetyl cysteine은 hydrogen peroxide에 의

해 유발된 조골세포의 증식, 분화, 무기질 침착 억제 상을 회복시킨다 (17,18). Kampferol은 구조골세포주인 MC3T3-E1

조골세포에서 자가 산화 단백질 당화 과정을 통해 활성 산소종을 생성하는 2-deoxy-D-ribose에 의한 조골 세포 기능

하를 감소시킨다 (19). Fisetin은 구조골 세포주인 MC3T3-E1에서 fluoride와 dexamethasone에 의해 유발된 산화 손상을

감소시키며 Metallothionein은 hydrogen peroxide에 의한 골수기질 세포로부터 조골 세포로의 분화를 억제하는 효과를 감소

시킨다 (20,21).

연구자들은 강력한 항 산화효과를 가지고 있다고 알려진 grape seed proanthocyanidin extract (GSPE)가 골세포 분화를

억제하고 조골세포 활성화를 진시키는 상을 찰하 다, 한 GSPE는 류마티스 염 환자의 fibroblast에서 RANKL

발 을 감소시켰다 (22).

이러한 결과는 항산화제가 골다공증 치료에 유용할 수 있음을 시사한다.

참고문헌

1. Thannickal VJ, Fanburg BL. Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol.

2000;279:L1005-28.

2. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological

functions and human disease. Int J Biochem Cell Biol 2007;39:44-84.

3. Almeida M. IBMS BoneKEy. Aging and Oxidative Stress: A New Look at Old Bone 2010;7:340-352.

4. Baek KH, Oh KW, Lee WY, Lee SS, Kim MK, Kwon HS, et al. Association of oxidative stress with postmenopausal osteopo-

rosis and the effects of hydrogen peroxide on osteoclast formation in human bone marrow cell cultures. Calcif Tissue Int.

2010;87:226-35.

5. Sugiura M, Nakamura M, Ogawa K, Ikoma Y, Yano M. High serum carotenoids associated with lower risk for bone loss

and osteoporosis in post-menopausal Japanese female subjects: prospective cohort study. PLoS One. 2012;7:e52643.

6. Makovey J, Macara M, Chen JS, Hayward CS, March L, Seibel MJ, et al. Serum uric acid plays a protective role for bone

loss in peri-and postmenopausal women: a longitudinal study. Bone. 2013;52:400-6.

7. Morton DJ, Barrett-Connor EL, Schneider DL, Vitamin C supplement use and bone mineral density in postmenopausal wom-

en, J. Bone Miner. Res. 2001:16;135-140.

8. Sakai E, Shimada-Sugawara M, Yamaguchi Y, Sakamoto H, Fumimoto R, Fukuma Y, et al. Fisetin Inhibits Osteoclastogenesis

Through Prevention of RANKL-Induced ROS Production by Nrf2-Mediated Upregulation of Phase II Antioxidant Enzymes.

J Pharmacol Sci. 2013 Mar 29. [Epub ahead of print]

9. Im NK, Choi JY, Oh H, Kim YC, Jeong GS. 6,4'-dihydroxy-7-methoxyflavanone Inhibits Osteoclast Differentiation and

Function. Biol Pharm Bull. 2013 Feb 19. [Epub ahead of print]

10. Moon HJ, Ko WK, Han SW, Kim DS, Hwang YS, Park HK, et al. Antioxidants, like coenzyme Q10, selenite, and curcumin,

inhibited osteoclast differentiation by suppressing reactive oxygen species generation. Biochem Biophys Res Commun.

2012:418:247-53.

11. Kim HJ, Chang EJ, Kim HM, Lee SB, Kim HD, Su Kim G, Kim HH, Antioxidant alpha-lipoic acid inhibits osteoclast

differentiation by reducing nuclear factor kappaB DNA binding and prevents in vivo bone resorption induced by receptor

activator of nuclear factor-kappaB ligand and tumor necrosis factor-alpha, Free Radic. Biol. Med. 2006:40;1483-1493.

12. Arai M, Shibata Y, Pugdee K, Abiko Y, Ogata Y. Effects of reactive oxygen species (ROS) on antioxidant system and

osteoblastic differentiation in MC3T3-E1 cells. IUBMB Life. 2007;59:27-33

13. Bai XC, Lu D, Bai J, Zheng H, Ke ZY, Li XM, Luo SQ. Oxidative stress inhibits osteoblastic differentiation of bone cells

by ERK and NF-kappaB. Biochem Biophys Res Commun. 2004;314:197-207.

14. Almeida M, Han L, Martin-Millan M, O'Brien CA, Manolagas SC. Oxidative stress antagonizes Wnt signaling in osteoblast

precursors by diverting beta-catenin from T cell factor- to forkhead box O-mediated transcription. J Biol Chem.

2007;282:27298-305.

15. Almeida M, Han L, Ambrogini E, Bartell SM, Manolagas SC. Oxidative stress stimulates apoptosis and activates NF-kappaB

in osteoblastic cells via a PKCbeta/p66shc signaling cascade: counter regulation by estrogens or androgens. Mol Endocrinol.

2010;24:2030-7.

16. Almeida M, Han L, Ambrogini E, Weinstein RS, Manolagas SC. Glucocorticoids and tumor necrosis factor α increase oxida-

tive stress and suppress Wnt protein signaling in osteoblasts. J Biol Chem. 2011;286:44326-35.

17. Chen RM, Wu GJ, Chang HC, Chen JT, Chen TF, Lin YL, Chen TL. 2,6-Diisopropylphenol protects osteoblasts from oxida-


tive stress-induced apoptosis through suppression of caspase-3 activation. Ann N Y Acad Sci. 2005;1042:448-59.

18. Ueno T, Yamada M, Igarashi Y, Ogawa T. N-acetyl cysteine protects osteoblastic function from oxidative stress. J Biomed

Mater Res A. 2011;99:523-31.

19. Suh KS, Choi EM, Kwon M, Chon S, Oh S, Woo JT, et al. Kaempferol attenuates 2-deoxy-d-ribose-induced oxidative cell

damage in MC3T3-E1 osteoblastic cells. Biol Pharm Bull. 2009;32:746-9.

20. Inkielewicz-Stepniak I, Radomski MW, Wozniak M. Fisetin prevents fluoride- and dexamethasone-induced oxidative damage

in osteoblast and hippocampal cells. Food Chem Toxicol. 2012;50:583-9.

21. Liu AL, Zhang ZM, Zhu BF, Liao ZH, Liu Z. Metallothionein protects bone marrow stromal cells against hydrogen per-

oxide-induced inhibition of osteoblastic differentiation. Cell Biol Int. 2004;28:905-11.

22. Park JS, Park MK, Oh HJ, Woo YJ, Lim MA, Lee JH, et al. Grape-seed proanthocyanidin extract as suppressors of bone

destruction in inflammatory autoimmune arthritis. PLoS One. 2012;7:e51377.


S148

Regulatory T Cells in HLA B27 Transgenic Rats

인하 학교 의과 학 내과학교실

권 성 렬

조 T 세포(Regulatory T cell)는 체내에서 다른 세포의 면역반응을 억제하는 역할을 한다. 이 역할은 과도한 면역반응을

막기 한 면역기능의 ‘자가조 ’ 기능에 해당한다. 조 T 세포는 여러 형태로 나타날 수 있으며 가장 잘 알려진 형태가

CD4+CD25+Foxp3+ 조 T 세포이다. 척추염은 공통된 임상 , 유 자 , 병리학 특성을 함께 하는 여러 질환을 포함한

다. 이 질환군에서 가장 표 인 질환이 강직척추염이다. 강직척추염은 척추와 말 염이 주로 나타나며 이외에

외 증상인 포도막염, 건선, 염증성 장염(Crohn’s disease 는 ulcerative colitis)이 나타난다.

척추염의 진단 치료의 비약 인 발 에도 불구하고 척추염의 원인 병인은 많이 밝 지지 않았다 (1). 사람 백 구

항원(Human leukocyte antigen, HLA) B-27이 척추염에서 요한 인자라는 것이 알려진 지 오랜 세월이 지났지만 그 역할이

명확히 밝 지지 않았다 (2).

HLA B-27이 척추염의 병인론에서 심 인 역할을 한다는 증거는 HLA B-27 유 자변형 쥐 모델에서 유래한다. 척추염

의 여러 염증성 증상이 HLA–B*2705과 사람 β2-microglobulin (h β 2m) 유 자 변형 쥐에서는 나타나지만, 조군인 HLA-

B*0702/h β2 유 자 변형 쥐에서는 나타나지 않는다 (3,4). HLA B-27 유 자변형 쥐 모델의 면역학 역할은 여러 면에서

밝 졌다.

첫째 정상 쥐에 척추염에 민감한 쥐의 미성숙한 조 세포를 주입하면 척추염이 유발되지만 성숙한 림 세포를 주입

하면 유발되지 않는다. 둘째, 가슴샘 유래 T 세포가 없는 nude HLA B-27 유 자변형 쥐는 척추염이 잘 생기지 않지만

분화무리 (cluster of differentiation, CD) 4 세포를 재구성하거나 가슴샘을 이식하면 척추염이 발생한다.

강직척추염을 비롯한 자가면역질환에서 CD4+CD25+Foxp3+ 조 T 세포가 감소되어 있다는 것은 여러 연구에서 보고하

다. 척추염의 주요유발유 자인 HLA B-27은 MHC class I 분자들의 일원이므로 CD8 T 세포에 항원을 달할 것으로 추측할

수 있다. 한 요즘 강직척추염과 연 성이 높은 것으로 보고되고 있는 endoplasmic reticulum aminopeptidase 1 (ERAP1)이

MHC class I 분자들의 발 에 여한다. ERAP1은 세포질 세망 (endoplasmic reticulum, ER) 내에 들어온 소멸될 정인 단백질

을 MHC class I에 알맞은 크기로 자르는 역할을 담당한다. ERAP1 polymorphism은 단백질의 aminopeptidase 기능변화에 의한

단백질 변성을 일으켜 비정상 peptide를 형성한다. 이 비정상 peptide가 MHC class I 분자에 발 하면 이상 면역반응을 일으킨

다.

ERAP1 polymorphism이 강직척추염 환자군에서 많이 보고되고 있다. 이 연구들은 CD8+ 조 T 세포의 존재와 강직척추

염에서 CD8+ 조 T 세포가 강직척추염에서 어떤 역할을 할 것이라는 것을 추측 한다. 강직척추염에서 CD8+ 조

T 세포와의 연 성에 해 앞으로 더 많은 연구가 필요하다.

참고문헌

1. Breban M, Said-Nahal R, Hugot JP, Miceli-Richard C. Familial and genetic aspects of spondyloarthropathy. Rheum Dis Clin

North Am 2003;29:575-94.

2. Lopez de Castro JA. HLA-B27 and the pathogenesis of spondyloarthropathies. Immunol Lett 2007;108:27-33.

3. Tran TM, Dorris ML, Satumtira N, Richardson JA, Hammer RE, Shang J, et al. Additional human beta2-microglobulin curbs

HLA-B27 misfolding and promotes arthritis and spondylitis without colitis in male HLA-B27-transgenic rats. Arthritis Rheum

2006;54:1317-27.

4. Hammer RE, Maika SD, Richardson JA, Tang JP, Taurog JD. Spontaneous inflammatory disease in transgenic rats expressing

HLA-B27 and human beta 2m: an animal model of HLA-B27-associated human disorders. Cell 1990;63:1099-112.

(2010. 1. 1∼2010. 12. 31)


[통풍연구회]

제1부 통풍


S151

환자에게 배우는 통풍이야기

경상 학교병원 류마티스내과

김 옥

S152 김 옥: 환자에게 배우는 통풍이야기


S157

Figure 1. The relationship between HFCS consumption and gout

prevalence in the United States.

한국인에서 Sugar-sweetened Soft Drink와 요산의 계

구가톨릭 학교 의과 학 류마티스내과

김 성 규

고요산 증은 성인 남성에게서 비교 흔히 발생하는 염증성 염인 통풍의 요한 요소이다. 통풍의 유병율과 발생

율은 지난 수십년 간 지속 으로 증가 추세에 있다. 더욱이 고요산 증은 다양한 사 질환과 심 질환의 험을

증가시키고, 더 나아가 이들 질환으로 인한 사망률 증가에도 련이 있는 것으로 알려지고 있다. 고요산 증의 증가 추세

는 비만, 당뇨와 같은 삶에 험한 요소로 작용하는 질환의 악화와 계가 깊은 것으로 보고 되고 있다. 하나 재미있는

사실은 고요산 증이 지나 수십년 동안 폭발 으로 소비량이 증가한 soft drink와 fructose의 섭취 증가와 상당한 련성이

있음이 최근에 여러 연구를 통하여 알려지고 있다.

미국내에서 fructose의 소비는 1967년 처음 소개 된 이후, 결정 상태의 설탕에 비해 사용방법, 수송의 용이성 등으로

지속 으로 소비가 증가되었다. High fructose corn syrup (HFCS)는 옥수수에서 fructose를 추출하여 HFCS-45, HFCS-55

등의 함량으로 사용되고 있다. 특히 미국 내에서 1977년에서 1997년 사이에 soft drink의 소비가 약 61% 정도 증가하는데,

이 HFCS가 단맛을 내는 첨가제로 사용되었다. 즉 soft drink의 소비량과 fructose의 소비가 거의 일치하고 있고, 이들 요인

이 요산 수치 통풍 발생의 증가에 크게 기여한 것으로 알려지고 있다(Figure 1).

Fructose의 사과정의 특징 에 하나로 요산이 사산물로 생성된다는 것이다. 식이로섭취된 fructose는 수용체인

GLUT2, GLUT5를 통하여 흡수되는데, fructose는 ATP (adenosine triphosphate)를 이용하여 AMP (adenosine monophosphate)

를 생성하고, 이는 IMP (inosine monophospate)로 변환되어 hypoxanthine를 거쳐 xanthine oxidase에 의해 요산이 생성되게

된다. 한 연구에서는 fructose를 섭취 1시간 내에 요산 농도가 2 mg/dL 증가하 다고 한다. 그리고 fructose가 요산

수치를 증가시키는 것 외에도 사과정 에 ATP를 소모하게 되므로 체내의 다른 사과정에도 잖은 나쁜 향을

수 있음을 시사한다.

최근에 여러 역학 연구에서 요산수치와 fructose의 련성에 한 보고가 있어 왔다. 특히 NHANES III 연구에서도

fructose가 많이 함유된 soft drink의 소비가 요산 수치의 증가에 여하고 있음을 보여 주고 있다(Figure 2). 반면에

fructose가 거의 함유되지 않은 diet soft drink의 경우

요산 수치와의 련성이 없음이 보고되었다. 이는 fructose

의 소비가 요산 수치의 증가와 한 연 이 있음을

시사하고 있다. 하지만 몇몇 연구에서는 fructose가 함유된

soft drink가 남자에게만 요산 수치를 증가시키고 여자에게

는 련이 없다는 보고와 함께, 단면 연구에서는 고요산

증의 유병율과는 련이 있으나, 향 연구에서는 발생

율에는 향이 없다는 보고들이 최근에 있어 왔다.

기존의 연구들은 주로 미국을 비롯한 북미의 연구 결과

들로 아시아 지역에서의 연구 결과는 거의 없는 실정이다.

본 연구는 남원, 양평, 고령 세 농 지역의 코호트 연구에

등록된 9,400명을 상으로 요산 수치와 식이(soft

drink, vitamin C, 고기, 해산물, 커피, 차, 과일)의 련성을

분석하고자 하 다.

S158 김성규: 한국인에서 Sugar-sweetened Soft Drink와 요산의 계

Figure 2. Correlation between serum uric acid level and soft drink (sugar sweetened and diet).

참고문헌

1. Choi HK, Mount DB, Reginato AM. Pathogenesis of gout. Ann Intern Med 2005;143:499-516.

2. Rho YH, Zhu Y, Choi HK. The epidemiology of uric acid and fructose. Semin Nephrol 2011;31:410-9.

3. Gao X, Qi L, Qiao N, Choi HK, Curhan G, Tucker KL, Ascherio A. Intake of added sugar and sugar-sweetened drink

and serum uric acid concentration in US men and women. Hypertension 2007;50:306-12.

4. Bomback AS, Derebail VK, Shoham DA, Anderson CA, Steffen LM, Rosamond WD, Kshirsagar AV. Sugar-sweetened soda

consumption, hyperuricemia, and kidney disease. Kidney Int 2010;77:609-16.

5. Choi JW, Ford ES, Gao X, Choi HK. Sugar-sweetened soft drinks, diet soft drinks, and serum uric acid level: the Third

National Health and Nutrition Examination Survey. Arthritis Rheum 2008;59:109-16.


S159

2012 ACR Guidelines for Management of Gout

앙 학교 의과 학 내과학교실 류마티스내과

송 정 수

S160 송정수: 2012 ACR Guidelines for Management of Gout


S165

통풍의 진료지침개발을 한 제안

한림 학교 성심병원 류마티스내과

김 아

통풍 치료의 실

통풍은 과거로부터 암이나 심장병, 뇌졸 등에 비해 그 요성이 부각되지 않아 환자는 물론 의사들도 통풍을 한낱

심한 염의 하나로 여겨졌으나 생명을 하는 질병과는 련이 없다고 생각되었다. 통풍 환자는 히 치료하면

정상 인 생활을 할 수 있는 반면 통풍 발작이 오면 염증만 치료하고 정작 요한 고요산 증을 제 로 리하지 않는

의사나 환자들이 많다.

우리나라의 실정도 크게 다르지 않아 국내 연구에서 통풍 환자의 요산억제제에 한 순응도와 그 결과에 미치는 인자를

찰하여 보고한 결과 통풍 치료의 순응도가 좋은 환자의 비율이 겨우 36.6%에 지나지 않는다는 사실이 밝 졌다. 한

순응도가 좋은 환자들의 평균 요산 농도조차도 6.44 mg/dL로 이 환자들마 제 로 치료가 되지 않고 있음을 지 하 다.

제안 1. 약물에 한 순응도가 38.3%에 지나지 않는 실에서 환자의 순응도를 높일 수 있는 실 방법은 무엇인가?

성 통풍의 치료

통풍 발작의 치료로 사용되던 표 인 약물은 콜히친과 비스테로이드항염제, 스테로이드 등이다. 치료기간은 성 발

작이 소멸될 때까지 투여한다. 에 발생한 발작의 경우는 내 스테로이드를 주사할 수 있다. Colchicine은 최근에

는 복용의 불편함과 독성 등의 우려로 사용이 감소하는 추세이다.

제안 2. 심한 성 통증 발작을 억제하는데 NSAID와 루코르티코이드를 함께 사용하는 경우 단독 치료보다 효능이

좋은가?

만성 통풍의 치료

1960년 반에 개발된 allopurinol은 통풍 치료의 명을 가져왔다. 많은 통풍 환자들이 allopurinol을 복용한 후에 통풍

발작의 빈도가 차 어들었다. 일부 환자들이 통풍에 과민반응을 보이고 극소수에서 치명 인 allopurinol 과민증후군

(allopurinol hypersensitivity syndrome, AHS)이 나타나는 바람에 allopurinol은 모든 환자들에게 안 하지 못하고 일부 환자들

에게는 험한 약으로 인식하게 되었다. 그 후 요산배설 진제인 sulfinpyrazone과 probenecid가 나왔으나 신장기능이 하

된 환자에게는 사용을 하지 못하고 요로결석 등의 부작용과 효과 부족으로 리 사용되지 못하 다. 그 후 개발된 요산배

설 진제가 benzbromarone이다. 이 약물은 청 요산을 잘 떨어뜨리며 신장기능이 약간 하된 환자에게도 안 하게 사용

할 수 있는 장 이 있으나 일부 환자에서 치명 인 간독성이 나타나서 미국 FDA에서는 승인을 하지 않아 재도 미국에

서는 이 약물을 사용하지 못하고 있다.

최근에 통풍 환자의 유병률이 증가하고 통풍의 병태생리가 조 씩 규명되면서 통풍 치료에 새로운 약물들이 많이 개발

되고 있다. Interleukin-1β (IL-1β)가 통풍의 발작에 요한 역할을 한다는 사실이 밝 지면서 IL-1β를 차단하는 약물들

이 통풍 발작의 치료에 사용하게 되었다. febuxostat은 allopurinol과 같이 xanthine oxidase를 억제하는 약물인데 allupurinol과

는 달리 purine 성분이 아니고 allopurinol sensitivity와 교차 반응이 없으며 xanthine oxidase를 더욱 선택 으로 차단하므로

효과가 강하고 하루에 한번 80 mg 한 알만 복용하면 되는 편리성을 갖고 있다. 한 여러 임상 시험에서 요산을 목표치까

S166 김 아: 통풍의 진료지침개발을 한 제안

지 우수하게 떨어뜨리는 효과와 안정성을 보 다. 한 요산용해제인 pegloticase가 2010년 9월에 미국에서 FDA 승인을

받고 매 이며 benzbromarone과 유사한 작용기 으로 요산배설 진을 일으키는 lesinurad가 임상 시험을 진행 이다.

제안 3. 다른 합병증이 없는 경우 통풍 발작이 몇 회 온 이후 요산강하제가 필요한가? 발작 빈도가 1년에 1회 정도로

낮은 경우에도 요산강하제가 필요한가?

제안 4. 통풍의 치료에서 기에 요산농도를 목표치까지 떨어뜨린 후 유지요법으로 요산 강하제의 감량이 가능한가?

(Dirty dish theory)

무증상 고요산 증의 치료

무증상 고요산 증은 치료하지 않는 것이 원칙이나 최근 심 질환이나 사증후군 등의 연 으로 요산 강하제의

응을 주장하는 연구자들도 있다.

제안 5. 무증상 고요산 증의 치료 응증이 있는가?

(2010. 1. 1∼2010. 12. 31)


[통풍연구회]

제2부 가성통풍


S169

부갑상선기능항진증에 의한 가성통풍; 증례

한양 학교 류마티스병원

재 범

칼슘피로인산염 침착질환(calcium pyrophosphate dihydrate deposition disease, 이하 CPPD)은 calcium pyrophosphate dihydrate

결정이 일으키는 모든 질환을 포함하는 넓은 의미의 용어로 연골석회화증의 가장 흔한 원인이다.

고령이 가장 흔한 험 요소이며 골 염이나 이 손상에서 흔히 나타난다. 드물게 사성 질환과 연 이 있는

경우가 있으며, 여기에는 색소침착증, 일차성 부갑상선기능항진증, 인산 증, 그리고 마그네슘 증 등이 알려져

있다.

연자 등은 10년 부터 간헐 인 무릎통증 종창으로 소염진통제와 내 스테로이드 주사 등으로 치료해왔던 47세

여자 환자에서 CPPD를 진단하 고, 기 질환으로 일차성 부갑상선기능항진증을 진단하고 수술 치료를 시행하 기에

증례와 함께 이를 고찰하고자 한다.


S170

CPPD 질환의 용어, 진단 치료에 한 유럽류마티스학회의 권고사항

순천향 학교 의과 학 내과학교실

찬 홍

Calcium pyrophosphate deposition (CPPD)은 fibrocartilage와 hyaline cartilage를 주로 침범하며, chondrocalcinosis (CC)의 가장

흔한 원인이다. 한, calcium pyrophosphate (CPP) associated arthritis는 RA와 gout에 이어 3번째로 빈도가 높은 염증성

질환이다.

2011년 유럽류마티스학회에서는 CPPD에 련된 용어를 통일하고 진단, 치료에 한 권고안을 제시하 다. 여기에서는

각각의 용어, 권고안과 그에 련한 간단한 근거 참고 사항을 살펴 보고자 한다.

CPPD 련 용어

CPP crystal: calcium pyrophosphate dihydrate crystal의 약칭(monosodium urate monohydrate를 sodium urate로 약칭하는 것과

유사하다.)

CPPD: CPP crystal이 발생하는 모든 경우를 포 하는 명칭

CC: cartilage calcification, 상진단이나 병리 소견으로 찰되는 경우

CPPD에 의해 나타나는 임상상

　- Asymptomatic CPPD: 임상증상이 없는 CPPD, CC 단독으로 있는 경우, CC가 동반된 OA가 여기에 속하며, 부분은

다른 목 으로 촬 한 상에서 우연히 발견되는 경우이다.

　- OA with CPPD: OA의 변화를 보이는 에 CC가 동반된 것이 상이나 병리 소견으로 확인된 경우

　- Acute CPP arthritis: CPPD 에 의해 발생한 성 자연치유성 활막염 (pseudogout 신 사용)

　- Chronic CPP crystal inflammatory arthritis: CPPD와 련된 만성 염증성 염

명된 험요인을 발 양상에 같이 기재함

　- 이 의 외상

　- 유 성/가족성 CPPD 침착 성향

　- 특수 질환( : hemochromatosis, primary hyperparathyroidism, hypophosphatasia, hypomagnesemia)

권고안의 근거수 강도

각각의 권고안은 level of evidence (LOE), visual analogue scale을 사용한 strength of recommendation 수(SORs)가 부여되

었다.

Level of evidence

　Ia: Meta-analysis of randomised controlled trials

　Ib: Randomised controlled trial

　IIa: Controlled study without randomisation

　IIb: Quasi-experimental study

　III: Non-experimental descriptive studies, such as comparative, correlation and case-control studies

　IV: Expert committee reports or opinion or clinical experience of respected authorities, or all


임상 양상(Table 1, proposition 1∼5)

(1) CPPD의 발 은 OA with CPPD의 양상이 가장 빈도가 높고, acute CPP arthritis, chronic CPP crystal inflammatory

arthritis의 양상을 띨 수 있다{IIb, SOR 90 (86∼94)}. CC는 단독으로 발생하거나 OA의 구조 변화와 동반할 수 있다.

CPPD가 동반된 OA는 동반하지 않은 경우에 비해 osteophyte의 형성이 더 빈번하고, 침범의 양상에서 차이가 나며,

좀 더 염증성 양상을 보인다. 드물게 주 CPPD나 비정형 CPPD는 tendinitis, tenosynovitis, bursitis, CPPD성 종괴

(tophi), 는 척추 침범에 의한 증상을 보일 수 있다.

(2) 극심한 통증, 부종, 압통이 있고 이러한 증상이 6∼24시간 안에 빠르게 진행하여 최고조에 이르고, 국소

인 발 을 동반하는 경우 acute CPP arthritis을 의심할 수 있으나 특이 인 증상은 아니다{IV, SOR 88 (84∼93)}.

(3) 결정 유발성 염을 시사하는 소견이 무릎, 손목 는 어깨 에 발생하고, 환자의 연령이 65세 이상인

경우 acute CPP arthritis의 가능성이 높다. 방사선학 인 CC의 존재와 고연령은 이러한 가능성을 증가시키지만 확정

진단을 해서는 결정의 확인이 필요하다{IIb, SOR 81 (74∼89)}. CC는 무릎 에서 가장 흔하고 손목, 어깨, 발목,

팔꿈치 순의 빈도를 보인다. Acute CPP arthritis는 무릎에 가장 흔하고 다음으로 손목, 어깨, 발목, 팔꿈치의 순으로 흔하게

발생한다. 동시에 2 군데 이상을 침범하는 경우는 10% 미만이고, 다발성 염의 양상을 보이는 경우는 드물다. 방사선

학 CC가 있다고 하더라도 활막액 검사에서 CPP가 반드시 찰되지 않을 수도 있으며, 따라서 확정 진단을 해서는

활액이나 조직에서 결정이 반드시 확인되어야만 한다.

CPPD의 험 요인으로는 나이가 가장 요하며, 50세 이 에는 드물지만 이후 극 으로 증가하는 양상을 보인다. 45세

이 에 발생한 경우, 다발 성으로 발생한 경우에는 가족성 질환이나 사성 질환의 성향이 있는지 확인해야 할 필요

가 있다.

(4) OA with CPPD는 특히 무릎 에 만성 인 증상을 일으키고 acute CPP arthritis의 증상을 동반할 수 있다.

OA with CPPD의 양상은 CPPD가 없는 OA와 비교하여, 염증성을 시사하는 소견과 증상이 더 심하게 나타나고, 비

형 인 침범을 모이며, 방사선학 으로 cyst나 osteophyte의 형성이 더 빈번한 특징을 보인다{LOE Ib/IIb, SOR

53 (38∼68)}. OA가 있는 경우 CPPD 발생의 험도는 2∼3배 증가한다. 비 형 인 OA와 CPPD간의 선후, 원인-결과

계에 해서는 알려져 있지 않다. OA with CPPD에서 침범되는 은 무릎, 손목, 어깨, 팔꿈치, 고 , 족(midtarsal)

의 순이고, 손의 경우에는 수지 (metacarpophalangeal) 특히 2번째와 3번째를 잘 침범한다.

(5) Chronic CPP crystal inflammatory arthritis는 만성 소수성 염이나 다발성 염으로 발 할 수 있고 신

S172 찬홍: CPPD 질환의 용어, 진단 치료에 한 유럽류마티스학회의 권고사항

염증 반응이 동반할 수 있다(CRP, ESR 상승). 이런 경우에는 RA를 포함한 다른 염증성 만성 질환에 한 감별

진단이 필요하게 된다. 방사선 소견이 진단에 도움이 될 수 있지만 확정 진단은 결정체의 확인을 통해서 가능하다

{IIb, SOR 83 (72∼93)}. 병원 환자를 상으로 한 chronic CPP crystal inflammatory arthritis의 연구의 결과를 보면, 부분

(89%)에서 단 염 는 소수성 염의 양상을 보이며 11%의 환자에서는 다발성 염의 발 을 보 다. 다 염으

로 발 하여 염증 소견과 신 증상을 동반하는 경우에는 RA를 포함한 만성 염증성 질환에 한 감별이 필요하게

된다.

진단(Table 2, proposition 6∼11)

활액의 검사

(6) CPPD의 확정 진단은 형 인 CPP결정(평행사변형, 세포내 치하는 경우가 부분이며 약한 양성 복굴 성

을 띤다.)을 활액이나 조직 검사에서 확인함으로서 가능하다{Ib, SOR 94 (90∼97)}. 결정의 수에 따른 정 기 은

없으며, 단 1개의 결정이 찰된 경우도 임상 으로 유의하게 취 한다. 결정체의 모양이 특이 일수록 더 진단의 신뢰성

이 높다.

(7) 진단이 되지 않은 염증이 노인 환자에서 무릎이나 손목에 발생한 경우에는 CPP와 요산 결정에 한 편

미경 검사를 모두 시행하는 것이 권장된다{IV, SOR 99 (97∼100)}. CPPD에 의한 염의 빈도가 높을 뿐만 아니라

비 형 인 발 을 보이는 경우도 있기 때문이다.

상 진단

(8) 방사선학 CC의 존재는 CPPD 진단에 도움이 되기는 하지만 CC가 없다고 해서 CPPD의 가능성이 배제되지는

않는다{IIb, SOR 97 (92∼102)}. CC와 활액 검사 결과가 일치하지 않는 경우가 많은 에 주의해야 한다. 확인된

CPP crystal arthritis에서 CC의 발견 빈도는 29∼93%로 상 환자군이나 검사를 시행한 에 따라 차이를 보일 수 있다.

방사선학 CC의 sensitivity와 specificity는 잘 연구되어 있지 않으나 18명을 상으로 한 소규모 환자 조군 연구의 결과

를 보면 sensitivity 0.29, specificity는 0.2로 낮았고, 손목의 CC를 가지고 있는 사람에서 활액내에도 CPP 결정이 발견

되는 것은 3%에 불과하 다. 이러한 불일치의 원인으로는 CC가 반드시 CPPD에만 특이 은 것은 아니며(basic calcium


phosphate도 CC를 보일 수 있다.), 단순 방사선 검사의 CC에 한 sensitivity가 낮으며, acute CPP arthritis가 아닌 경우

(특히 무증상 CC에서 cartilage fibrillation에 의한 결정체의 강내 유리가 일어나지 않은 경우), 연골이 많이 소실된

상태여서 CC를 찰하기 힘든 경우, 결정체 자체가 작고, 특이 학 특성이 결여되어 있는 경우 등이 있기 때문으로

풀이된다.

(9) 음 소견은 고에코의 밴드가 hyaline cartilage내에 찰되거나 는 고에코의 반짝거리는 의 형태로 fi-

brocartilage내에 보여질 수 있다. sensitivity와 specificity가 단순 방사선 소견에 비해 우월하다{IIb, SOR 78 (70∼87)}.

CC가 hyaline cartilage내부의 고에코의 선형 침착이나 fibrocartilage내의 부정형 는 구형의 침착으로 보이는 반면, 요산

결정의 경우 연골의 표면에 고에코의 선형 침착으로 찰된다. 무릎 에서의 음 검사의 sensitivity는 96.4∼

97.6%, specificity는 68.7∼86.7%로 단순 방사선 검사에 비해 CPPD를 진단하는데 더 민감하다.

험요인, 동반질환에 한 검사

(10) Acute CPP arthritis과 퍠 증이 동반될 수 있다. 따라서 감염이 의심될 경우 CPP crystal 이나 CC가 확인된

경우라도 미생물학 검사가 시행되어야 한다{III, SOR 96 (93-100)}.

(11) CPPD가 있는 환자에서는 험 요인이나 연 질환이 있는지 여부에 한 조사가 필요하다(OA, 이 의 외상력,

유발할 수 있는 사성 질환-hemochromatosis, primary hyperparathyroidism, hypomagnesaemia, 가족성 질환). 특히

55세 미만의 은 연령층의 환자이고, 다발성 CC가 있는 경우 사성 질환이나 유 질환의 가능성이 높다{Ib/IIb,

SOR 94 (89∼99)} (Table 3). 연령증가와 손상은 OA와 CPPD의 공통 험 인자이다. 한 OA의 연골은 calcium (basic

calcium phosphate를 포함한) 결정의 침착을 유발할 수 있고, 반 로 CPPD는 OA의 연골 손상을 더 증폭시킬 수 있다.

성별이 CPPD에 향을 주는 지에 해서는 이견이 있다. BMI 증가는 OA의 요 험 요인이기는 하지만 CPPD와

연 이 있다는 증거는 없다. 이 의 손상은 CPPD를 유발할 수 있다. 무릎 반월 수술을 받은 환자의 후향성 코호트

조사에 의하면, CC의 험도가 수술을 받지 않은 반 측 정상 에 비해 5배 높았다는 보고가 있다. 고 험 요인이

될 수있는 사성 질환 - hemochromatosis, hyperparathyroidism, hypomagnesaemia 등-에 한 선별 검사가 고려되어야 한다

(calcium, phosphorus, magnesium, alkaline phosphatase, ferritin, Iron, transferrin, thyroid stimulating hormone). CC가 가족 집

성을 보인다는 증거는 없으나 가족력이 있는 경우 좀 더 조기에 발생할 수 있다.

S174 찬홍: CPPD 질환의 용어, 진단 치료에 한 유럽류마티스학회의 권고사항

치료(Table 4)

Table 4. LOE and SOR: order according to topic (general, acute attacks, prophylaxis and chronic CPPD management)

(1) 한 치료를 해서는 약물 치료 외에 비약물 치료가 병용되어야 하며, 임상상, 일반 인 험요인(나이,

동반질환) 유발하는 사성 질환에 따라 조정이 필요하다{IV, SOR 93 (85∼100)}. 무증상의 CC는 노화와 련되어

나타나는 정상 인 변화인 경우가 부분으로 치료를 요하지 않는다. Acute CPP arthritis의 경우 치료의 주목표는 빠른

증상의 경감이다. 이에 반해, 발작간기의 환자나 OA가 동반된 경우, 만성 증상이 있는 경우 증상과 장애를 경감시키는

것을 목 으로 교정가능한 험 요인을 찾고, 구조 손상의 진행을 막는 장기간의 치료 계획의 수립이 필요하다. Acute

CPP arthritis의 치료에 해서는 무작 비교- 조군 임상연구에 의한 결과가 거의 없으므로 주로 gout의 치료에 근거한

치료법이 권장되고 있다.

(2) 얼음이나 cool pack의 용, 휴식, 흡인과 강내 장기 작용성 스테로이드 주사 등이 사용될 수 있다.

상당수의 환자에서는 이 정도의 치료로 효과를 볼 수도 있다 {IIa-IV, SOR 95 (92∼98)}. 부분의 경우에서 흡인

만으로 증상이 경감되며, 추가 인 치료가 필요하지 않다. 스테로이드 주사의 경우, 단 염이나 소수 염의

형태로 발생한 경우에 선호된다.

(3) NSAID, 용량 colchicine 사용이 acute CPP arthritis의 효과 인 치료로 사용될 수 있으나, 독성 동반질환

때문에 사용에 제약이 있을 수 있고, 노인 환자일 수록 더 주의가 필요하다{Ib-IIb, SOR 79 (66∼91)}. Colchicine의

경우, gout에서 사용되는 고식 인 용법 로 사용할 경우 부작용의 빈도가 높기 때문에 0.5 mg을 3∼4회/일, loading dose

없이 복용하는 용량 요법이 추천된다. 사용기간은 증상 완화와 부작용에 따라 결정된다. Colchicine 정맥주사의 경우

독성의 문제로 권장되지 않는다.

(4) 단기간 tapering course의 경구 스테로이드 는 스테로이드나 ACTH의 주사 요법이 강내 스테로이드 주사

가 불가능한 경우에 사용될 수 있고 colchicine 는 NSAID의 체제로서 사용될 수 있다{IIb-III, SOR 87 (76∼97)}.

스테로이드는 노인 환자에서 특히 NSAID나 colchicine에 한 기 사항이 있는 경우 고려될 수 있다. 스테로이드 강

내 주사는 단 염이나 소수성 염이 있는 경우에 유용하며, 경구 스테로이드나 스테로이드, ACTH 주사는 다발성

염 환자에서 다른 치료의 체제로 이용될 수 있다. 스테로이드 사용의 다른 이 으로는, 질병 기 빠른 증상 호 에

있어서 NSAID보다 더 효과 일 수 있다는 것이다.

(5) 자주 재발하는 acute CPP arthritis의 방에는 용량의 colchicine (0.5∼1 mg daily)이나 용량 경구 NSAID를

사용할 수 있다{IIb-IV, SOR 81 (70∼92)}. Gout와 달리 방요법에 있어서 NSAID와 colchicine 어떤 것이 더 우월한지

에 해서는 확실하지 않다.

(6) 치료의 목 이나 치료 방법의 선택은 CPPD가 동반된 OA와 동반되지 않은 OA 간에 차이가 없다{Ia, SOR 84

(74∼94)}. CPPD와 OA가 동반된 경우, 그 지 않은 경우보다 좀 더 심한 염증 반응이 동반되고, 임상 양상이나 방사선학

진행 면에서 다른 후를 보여 가능성이 높으나 치료 방법에서는 근본 으로 OA의 치료와 같다. 고분자량 hyaluronan의

강 내 주사는 성 발작을 유발할 가능성이 높으므로 주의가 필요하다.

(7) Chronic CPP crystal inflammatory arthritis의 경우, 선호되는 치료는 경구 NSAID 단독( 장 궤양에 한 방

약제는 포함) 는 colchicine과의 병용, 용량 스테로이드, methotrexate, hydroxychloroquine 순이다{Ib-IV, SOR 79


(67∼91)}. MTX는 고식 인 치료에 반응하지 않는 심한 CPPD의 치료로 시도되고 있다. 용량 methotrexate (5∼10

mg/week)를 만성 증상과 acute CPP arthritis이 동반된 치료 불응성 CPPD에 사용한 uncontrolled trial의 결과에서 통증, 부종

압통의 완화와 성 발작의 빈도를 히 억제하 다는 보고가 있다. 재 더 큰 규모의 methotrexate treatment trial이

진행 에 있다. 이외에도, Hydroxychloroquine, NLRP3 inflammasome interleukin 1β pathway를 차단하는 치료 등이 연구되

고 있다. 용량 스테로이드의 사용에 해서는 임상연구에 의한 근거는 없는 상태로 문가 견해에 의해 추천되고 있다.

Radiocolloid (yttrium-90)을 이용한 radiosynovectomy는 소규모 연구에서 통증 경직감 감소에 효과를 보인 것으로 되어

있으나 임상연구를 통해 축 된 근거가 어 아직 추천되고 있지는 않다.

(8) Hyperparathyroidism, hemochromatosis, hypomagnesaemia 등이 발견되는 경우에는 치료가 필요하다{IIb, SOR 89

(81∼98)}.

(9) 재로서는 CPP 결정의 형성을 억제하거나 결정의 분해를 유도할 수 있는 치료는 없는 상태이며, 무증상성

CC 에 한 치료는 필요하지 않다{IV, SOR 90 (83-97)}. Magnesium, pyrophosphate 농도를 조 하는 약제(probenecid,

polyphosphate, pohsphocitrate 등)을 사용해서 CPP 결정의 융해나 형성을 억제하는 치료가 시도 되고 있으나 아직은 이론이

나 실험 인 수 에 머무르고 있다.

참고문헌

1. Zhang W, Doherty M, Bardin T, Barskova V, Guerne PA, Jansen TL et al. European League Against Rheumatism recom-

mendations for calcium pyrophosphate deposition. Part I: terminology and diagnosis. Ann Rheum Dis. 2011;70(4):563-70.

2. Zhang W, Doherty M, Pascual E, Barskova V, Guerne PA, Jansen TL et al. EULAR recommendations for calcium py-

rophosphate deposition. Part II: management. Ann Rheum Dis. 2011;70(4):571-5.

3. Mecker MA, Ryan LM. Clinical manifestations and diagnosis of calcium pyrophosphate crystal deposition diseases. In:

UpToDate, Basow, DS (Ed), UpToDate, Waltham, 2013.

4. Doherty M and Abhishek A. In: Hochberg MC. Ed. Rheumatology. 5th edition. p.1875-87, Philadelphia, Elsevier, 2011.

(2010. 1. 1∼2010. 12. 31)


[척추관절염연구회]

제1부


S179

Is AS a Genetic Disease?

Division of Rheumatology, Daejeon Rheumatoid & Degenerative Arthritis Center, Chungnam University Hospital

Seung Cheol Shim

Ankylosing spondylitis (AS) is a heritable disease with 90% of susceptibility being attributable to genetic factors. The modes

of inheritance are best studied by analysis of the recurrence risk among families. The recurrence risk is defined as the chance

that a genetic disease presenting in a family will recur in that family to affect another person. The recurrence risk for AS is

63% among monozygotic twins and 8.2% among first-degree relatives. These figures are high in comparison with a recurrence

risk of 0.1% in the general population. The best-fit inheritance model of AS is an oligogenic model with multiplicative interaction

between loci. In other words, the risk in people who carry several susceptibility loci equals the product of the risks associated

with each locus alone. According to recurrence modeling conducted in the year 2000, up to nine loci are involved in AS.

HLA‑B27 is an allele of the HLA-B locus in the class 1 region of human MHC. In most populations of the world, HLA-B27

is present in ＞90% of patients with AS, but in ＜10% of the general population. The almost universal presence of HLA-B27

in AS has led to it being described as an essential gene for AS. In support of the arthritis associated nature of the gene, HLA-B27

transgenic rats develop a disease that resembles an arthritis of the spondyloarthritis family. Although the biology of HLA-B27

has been the focus of a great deal of cutting-edge research over the past four decades, the reason for its association with AS

is still a matter of speculation. It is imperative that we close the gap between basic science and translational medicine in this

field. Furthermore, of the HLA‑B27-positive individuals in the general population, only 5% develop AS, and HLA-B27 accounts

for just 25% of disease hereditability. Hence, additional genes must be involved.

To date, seven loci have been identified and validated through genome-wide association studies. These loci encode the following

molecules: HLA-B27, endo plasmic reticulum aminopeptidase 1 (ERAP1, previously known as TNF-receptor-shedding amino-

peptidase regulator 1 or ARTS1), interleukin-23 receptor (IL-23R), interleukin-1 receptor type 2 (IL-R2) and anthrax toxin receptor

2 (ANTXr2, also known as capillary morphogenesis gene 2 protein or CmG2); the remaining two loci do not encode gene sequences.

The most promising future studies will be those that define the structural variants of these AS genes and investigate how these

variations affect downstream and upstream pathways. None of the genes identified so far is directly related to bone erosion or

syndesmophyte formation. Studies investigating these processes have emerged to be of the highest clinical priority and have al-

ready led to the identification of major pathways that are involved in the pathogenesis of AS.

References

1. Wellcome Trust Case Control Consortium; Australo-Anglo-American Spondylitis consortium (TASC); Burton, P. R. et al.

Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat. Genet.

2007;39:1329-37.

2. Australo-Anglo-American Spondyloarthritis consortium (TASC); Reveille, J. D. et al. Genome–wide association study of anky-

losing spondylitis identifies non-MHC susceptibility loci. Nat.Genet. 2010;42:123-7.

3. Thomas, G. P. & Brown, M. A. Genetics and genomics of ankylosing spondylitis. Immunol.Rev. 2010;233:162-80.

4. Genovese, M. C. et al. LY2439821, a humanized anti-iL-17 monoclonal antibody, in the treatment of patients with rheumatoid

arthritis. Arthritis Rheum. 2010:62;929-39.

5. López de Castro, J. A. The HLA-B27 peptidome: building on the cornerstone. Arthritis Rheum. 2010:62;316-9.

6. Tam, L.-S. Gu J, Yu D. Pathogenesis of ankylosing spondylitis. Nat. Rev. Rheumatol. 2010;6:399-405.

7. McHugh K, Bowness P. The link between HLA-B27 and SpA-new ideas on an old problem. Rheumatology 2012;51:1529-39.


S180

건선 염 정말 드문가? -역학, 진단, 치료

가천 학교 의학 문 학원 길병원 류마티스내과

백 한 주

건선 염은 건선에 동반된 염증성 염으로 정의된다. 환자의 부분은 청 류마티스인자가 음성이다. 증상 면에

서 염증성 염의 일반 인 특징을 공유하지만, 류마티스 염보다 압통이 덜한 경향을 보이며, 심각한 통증 없이

변형으로 나타나기도 한다.

침범 형태는 통 으로 말단 염, 비 칭 소수성 염, 칭 다발성 염, 단 염, 척추 염의

5가지로 분류한다. 최근 문헌에 따르면 가장 흔한 형태는 다발성 염, 소수성 염 순이며, 우리나라에서는 척추

염이 가장 흔한 형태로 보고된 바 있다. 말단 염과 단 염은 건선 염의 가장 특이한 형태이다. 상당수 환자에

서 침범 형태는 복합 으로 나타나고 시간에 따라 변하기도 한다.

건선 염은 다른 척추 염과 마찬가지로 부착부염, 건 염, 지염, 포도막염 건선 환자에서 흔히 발견되는 조갑함몰이

나 조갑박리를 동반하기도 한다. 건선 염에서 조갑 이상은 말단 염과 흔히 동반되며, 피부 질환의 범 와

정도와 상 계를 보인다. 부분의 환자에서 염이 건선 발병 이후에 생기지만 15% 내외의 환자에서 건선보다 염

이 먼 생기며, 이런 경우엔 진단이 쉽지 않다. 건선 건선 염 환자는 이상의 증상 이외에도 심 계 질환, 사성질환,

장염과 같은 합병증을 종종 동반하며, 이들의 발병은 TNF와 같은 사이토카인이나 면역염증세포가 매개하는 염증 기 을

공유하고 있다. 이에 따라 최근 건선은 피부, , , 장 등 다기 을 침범하는 일련의 만성염증질환으로 이해된다.

건선 염 환자의 상당수 환자에서 방문 당시부터 방사선학 이상 소견을 보인다. 가장 특징 인 이상 소견은 말단

의 미란 신생골 형성이 함께 존재하는 것이다. 이 외에도 말단 의 용해, 부착부의 솜털 같은 골막염 소견 신생골

형성, 각각의 의 심한 괴, “pencil-in cup” 모양, 한 환자에서 분해와 골강직의 공존 등이 특징 등이 있다.

건선 환자에서 염증성 이 있으면 건선 염으로 진단될 가능성이 높지만, 건선과 염이 같이 있다고 모두 건선

염인 것은 아니다. 건선 염의 진단은 특징 인 임상 , 방사선학 양상에 기 하여 이루어진다. 건선 염을

분류하기 해 고안된 CASPAR 분류기 은 염증성 근골격계 증상이 있는 환자에서 건선 염을 진단하는데 90% 이상

의 민감도와 97% 이상의 특이도를 보여주었다. 최근 조기 염 코호트에서 시행한 한 연구에 의하면 ASAS 말 형

척추 염 분류기 은 CASPAR 분류기 보다 건선 염에 한 민감도가 떨어지는 것으로 조사되었다.

건선 염은 괴로 인한 장애를 래할 수 있는 질환이다. 치료는 피부 질환의 염증을 조 하고 손상을

방하는데 맞추어져 있다. 에 한 약물치료는 보통 NSAID로 시작하고, 여기에 반응이 없으면 MTX, Leflunomide,

Sulfasalazine같은 비생물학 DMARD를 투여한다. 이상의 비생물학 DMARD로도 호 이 없으면 TNF 차단제와 같은

생물학 제제를 추가하거나 비생물학 DMARD의 병용요법을 사용한다. 스테로이드의 경구요법은 피해야 한다. 아직까

지 비생물학 DMARD나 TNF 차단제가 장애를 방하는지에 한 장기 인 자료는 부족하다.

한국에서 건선 염의 발생률과 유병률에 한 자료는 아직 없다. 외국 자료에 의하면 건선 염 발생 빈도에 있어서

남녀차이는 없으며, 발생률은 100,000명 당 6, 유병률은 1,000명 당 1∼2로 알려져 있다. 보고에 따라 발생률과 유병률의

차이가 큰데 이것은 건선 염의 정의와 지역 차이에 기인한 것으로 생각된다. 같은 이유로 건선 환자에서의 건선

염의 발병 빈도는 4∼30%로 보고마다 차이가 크다. 우리나라에서 건선 환자 건선 염의 빈도는 10% 내외로 보고되

어 있다. 서구에 비해 우리나라 건선 유병률은 낮다고 알려져 있지만 최근 속히 증가하는 양상을 보이고 있어 건선

염 환자도 증가할 것으로 추정된다. 최근 외국의 한 연구는 피부과를 다니는 건선 환자의 29%에서 진단받지 못한 건선

염을 갖고 있음을 발표하 다. 건선 염 환자의 진단과 치료의 발 을 해서는 건선 염에 한 새로운 인식

한 진단기 의 용과 더불어 류마티스내과와 피부과의 긴 한 조가 필수 이다.

(2010. 1. 1∼2010. 12. 31)


[척추관절염연구회]

제2부


S183

Recent Update in MRI Studies for Axial Spondyloarthritis

SMG-SNU Boramae Medical Center

Kichul Shin

　The recent changes in diagnosing or classifying spondyloarthritis (SpA) mainly lies in the advances in imaging modalities

for SpA. Especially, magnetic resonance imaging (MRI) of the axial spine provides further information that we could not appre-

ciate through plain imaging or computed tomography of that same region. In the sacroiliac joint, MRI findings of bone marrow

edema, enthesitis help to diagnose inflammatory lesions; spine MRI better depicts spondylitis, spondylodiscitis, enthesitis, arthritis

of costovertebral joints or zygoapophyseal joints, and enthesitis of spinal ligaments. The ASAS/OMERACT MRI group has re-

cently published a paper showing how to interpret or define such lesions in MRI. However, there is still research in need to

fully understand the sequential changes of spinal inflammation to new bone formation. Recent peer-reviewed publications regarding

MRI studies in SpA will be introduced, hopefully summarized well enough to stimulate discussions of where MRI lies in our

daily practice, and future directions for research.


S184

강직성 척추염의 치료 리


김 태 종

서 론

강직성척추염은 청음성 척추 염의 가장 흔한 형태로 천장 과 척추를 침범하여 척추변형 강직을 일으킬 수

있는 만성 염증질환이다. 아직까지 명확하게 규명된 병인은 없지만 여러 가설 HLA-B27과의 연 이 가장 요한 요인

으로 여겨지고 있다. 질환이 염증에서 시작하므로 염증 조 이 일차 치료 목 이 되지만 여러 가지 복합 인 요인을

가지고 있어 축성 만 침범하거나, 말 을 같이 침범하거나 혹은 외 침범으로 포도막염이 오기도 하기 때문에

치료는 각각의 패턴에 따라 결정해야 한다. 따라서 본 자는 최근까지 진행된 강직성 척추염의 치료법과 이에 한

치료 평가 항목을 소개해 보고자 한다.

본 론

강직성 척추염의 치료는 다른 만성 염증성 류마티스 질환의 치료와 마찬가지로 염증을 조 하여 의 운동범 를

유지하여 일상생활을 하는 것이 목 이다.

비약물 치료

1) 환자의 교육

강직성척추염의 경우 척추의 강직이 일어나는 경우는 10-30%정도로 알려져 있고 나머지는 일상생활이나 운동에도 지장

이 없는 것으로 보고되고 있다. 따라서 환자의 교육 시 환자의 올바른 자세와 진행 정도에 맞는 운동을 교육하고 잘

리할 시 일상생활에 지장이 없음을 강조하여야 한다. 흡연은 폐기능을 떨어뜨리고 골다공증을 유발함으로 반드시 연

하도록 교육한다. 올바른 자세를 해서는 항상 허리를 꼿꼿이 세우도록 하며 경추의 굴곡변형을 막기 해 작업 시

모니터 등을 높이에 맞도록 조 하고, 수면 시 되도록 통증을 느끼지 않는 정도의 최 한 딱딱한 매트에서 낮은 베개를

베도록 교육한다.

2) 물리치료

물리치료로도 환자의 운동기능에 많은 향상이 가능하므로 진단과 동시에 운동방법과 바른 자세를 교육해야 한다. 운동

치료는 척추의 굴 변형을 막기 해 척추의 신 운동과 회 운동을 주로 교육한다.

3) 수술 치료

약물로 조 하지 못하는 의 기능 손상이 왔을 시에는 수술로 의 운동범 를 호 시키거나 자세를 교정함 수술이

필요한 경우는 고 의 손상으로 일상생활이 힘들 경우 고 치환술이 가능하며, 척추의 굴곡변형으로 정면을 보기

힘들고 폐활량이 어 호흡이 힘들 때, 수면 시 머리가 바닥에 닿지 않아 수면이 불가능할 시 척추교정술을 시행한다.

약물 치료

1) 비스테로이드성 항염증제(Non-steroidal anti-inflammatory drug)

재에는 비스테로이드성 항염증제 간에는 환자 개개인에 따라 차이가 있을 수 있지만 어느 것이 더 우월하다고 말할

수 없는 것이 론이다. 2005년 무작 시험을 통해 강직성 척추염에서 통증이 있을 때만 복용하는 군보다 지속 으로

복용하는 군이 척추강직 변화가 음을 보여 주었고 독성에도 차이가 없음을 발표하 다. 하지만 염증성 장질환이 동반된


경우에는 항염제 사용에 주의를 요한다.

2) 항류마티스 약제

(1) 설 살라진(Sulfasalazine): 메타분석결과를 살펴보면 재 말 염이 동반된 경우에 추천되고 있다. 투여는 하루

500 mg을 첫 주간 투여 후 하루에 500 mg씩 증량하여 하루 2∼3 g으로 투여한다.

(2) 메소트 세이트(Methotrexate): 2007년 meta-analysis data에서 강직성 척추염 치료에 효과 근거가 없는 것으로 보고

하 고 ASAS 권고 사항에서도 추천되지 않는다.

(3) 루노마이드(Leflunomide): 몇가지 연구는 있지만 효과가 거의 없는 것으로 추천되지 않는다.

(4) 스테로이드(Steroid): 국소 스테로이드 주사는 말 염이나 통증이 있는 골부착염에 도움이 되는 것으로 되어

있으나 신 스테로이드의 투여는 추천되지 않는다.

(5) Pamidronate, Thalidomide: Pamidronate는 용량 의존성으로 항염증제에 반응이 없는 환자에서 도움이 되는 것으로 보고

되었고, thalidomide는 도움이 되나 높은 부작용 빈도를 보이고 모두 효과를 입증하기 한 규모 연구가 부족하다.

(6) 생물학 제제: 재 효과가 인정되어 사용되는 생물학 제제는 infliximab, etanercept, adalimumab 3가지가 있다. 이

약제는 다른 질환에서 보다 강직성 척추염 증상 완화에 탁월한 효과가 있어 리 사용되고 있으며 장기간의 효과는

세 가지 약제 사이에 큰 차이는 없는 것으로 보고 있다. 2006년 ASAS 가이드라인에는 개정된 뉴욕진단기 으로

진단된 강직성 척추염 환자의 경우 3개월 동안 2종류이상의 비스테로이드성 항염증제 치료에도 질병 조 이 안될

때 사용을 권고하 으나 2010년 개정내용에는 개정된 뉴욕 진단 기 뿐만 아니라 ASAS 축성 척추 염 분류 기

도 포함하 으며 4주 동안에 2종류 이상의 비스테로이드성 항염증제 치료에도 질병 조 이 안될 때 사용하도록

하여 조기치료의 요성을 강조하 다. 투여하는 방법에 따라 반응이 빠르고 늦을 수 있으며 잠복결핵의 활동성

결핵으로의 이환은 monoclonal antibody제제가 높은 것으로 알려져 있지만 포도막염이 동반된 환자에서는 monoclonal

antibody 제제가 추천된다. 이들 종양괴사인자 억제제가 환자의 통증, 운동범 , 삶의 질과 기능에 탁월한 효과를

보이지만 질병의 특징인 골형성 진행을 방지하는가에 한 물음에는 오랜 기간의 추척 찰이 필요한 실정이며

아직까지 답을 못하고 있다.

최신 치료제 연구 동향

TNF 차단제의 탁월한 효과에도 불구하고 이러한 약제에 반응이 없는 환자들에 한 치료 안이 아직까지 없는 상태이

기 때문에 TNF 차단제 치료 실패 이후에 사용할 수 있는 새로운 생물학제제에 한 연구가 활발히 개시되고 있다. 따라서

최근에 시행되고 있는 생물학 치료제제에 한 임상 연구들의 동향에 해 간략히 살펴보고 앞으로 치료제로서의 가능성

이 있는 약제들에 해 소개해 보고자 한다.

1) CD20+B세포 억제제(Rituximab): 악성 림 암 류마티스 염에서 사용되는 약제로 강직성 척추염에 한 연구도

진행되었는데 이 연구에서는 TNF차단제를 사용하지 않은 환자군이 TNF차단제 치료 실패 환자에 비해 BASDAI,

ASAS20, ASAS40 치료반응률이 의미 있게 호 된 결과를 보여 주었다. 이 연구에서의 피험자 수가 각각 10명으로

매우 어 규모의 추가 임상 연구가 필요한 실정이지만 TNF차단제 실패환자 보다는 TNF차단제를 사용할 수 없는

환자들에게서 기 사용이 고려 될 수 있음을 제시하 다.

2) T세포 조 제(Abatacept): CTLA-4 면역 로블린을 이용한 T세포 면역활성 억제를 통해 류마티스 염 약제로 사용

되고 있으나 강직성 척추염에서는 증상 호 효과를 보여주지 못하 다.

3) IL-1 차단제(Anakinra): 활동성 강직성 척추염 환자에서 6개월 동안 IL-1 차단제 치료 반응률이 치료 에 비해 질병활

성도 척도인 BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), CRP, 염 모두에서 효과를 나타내지

못했다.

4) IL-12/23 차단제(ustekinumab, briakinumab): Naive T세포가 T helper1/T helper17세포 분화에 여하는 염증사이토카인

인 IL-12, IL-23차단 단클론 항체는 건선 염과 크론씨병에 좋은 효과를 보여주어 비슷한 병인을 가지는 강직성

척추염에서도 효과 일 수 있다는 가능성을 제시하 다. 따라서 추후 강직성 척추염 환자에서의 임상 연구가 필요하

겠다.

5) IL-6 차단제(tocilizumab): IL-6 수용체 차단제는 활동성 강직성 척추염에 효과 이라는 보고와 효과가 미미하다는

비 임상 시험 결과가 있어 추후 결과를 좀더 지켜 야 하겠다.

6) IL-17차단제(Secukinumab): 류마티스 염에서 최근 이슈가 되고 있는 표 염증 사이토카인 IL-17에 한 차단

항체의 비데이터에서는 ASAS20치료 반응률이 61%로 조군의 17%보다 좋은 결과를 보여 주어 재 진행되는

결과에 따라 새로운 치료제로 두 될 가능성이 있다.

S186 김태종: 강직성 척추염의 치료 리

Figure 1. 강직성척추염 치료 후의 평가를 한 ASAS 반응

기 .

치료의 평가방법

1) 환자 증상 활성도 평가

(1) 통증, 피로감, 환자평가 의사평가: 환자가 느끼는 통증 정도를 측정하는 것으로 밤에 느끼는 척추 통증이 요하고,

환자가 느끼는 피로감의 변화를 측정하는 것이다. 환자평가와 함께 의사평가를 VAS (visual analog scale)로 측정한다.

(2) 척추운동: 재 증상 정도와 과거부터 진행되어온 변형에 의한 운동제한이 반 된다. 강직성척추염 문가모임에서

는 치료 후 평가를 해 BASMI를 사용하고, x-선 검사 후 척추변형 수(mSASSS etc) 변화와 BASMI결과를 비교해

서 사용하고 있다.

(3) 말 염 골부착부염: 강직성척추염이 척추를 주로 침범하는 질환이기는 하나 말 염 침범 한 흔하게

동반된다. 44개 을 측정하며 부종, 압통에 해 ‘있다, 없다’로 평가한다. 골부착부염은 주로 Mander enthesis index

(MEI)로 66부 를 0-3 으로 수화 하고 총 수가 90 을 넘지 않게 사용하고 있다. 측정 해야 할 부 가 무

많고, 측정의 어려움으로 간편하게 만든 MASES (Maastricht Ankylosing Spondylitis Entheses Score), BEI (Berlin

Enthesitis Index)를 사용하려는 경향이 있다.

(4) BASDAI, ESR, CRP: 통증, 피로감, 강직 등 불편함을 종합해서 BASDAI를 사용한다. 말 염이 주 증상인 경우엔

문제 이 많으며, 척추증상만 있는 경우에는 척추증상 문항만을 이용하려는 움직임이 있다. ESR, CRP는 염증을 반

할 수 있는 요한 검사이지만 약 40% 환자에서 강직성척추염 증상을 반 하지 못하고, 어느 검사가 우월하다고

결론 내린 것도 없다.

2) 척추 등 변형 상태 평가

척추 등 의 비가역 인 변화가 온 것을 의미하며 syndesmophytosis, ankylosis, erosion 등이 여기에 속한다. 강직성척추

염이 서서히 진행되는 질환이라 평가에 어려움이 있지만 가장 리 사용되는 것은 modified stoke ankylosing spondylitis

spinal score (mSASSS)와 Bath ankylosing spondylitis radiographic index (BASRI)이다. 최근 임상연구에서는 mSASSS를 더

많이 사용하고 있다.

3) 육체 인 기능과 삶의 질 평가

(1) 육체 인 기능: 육체 인 변형으로 생활에 제한이 있는지 여부를 단하는 평가방법으로 Bath ankylosing spondylitis

functional index(BASFI)와 Dougados functional index (DFI)가 있다. BASFI에는 환경 인 문항이 추가되어 있다. HAQ를

강직성척추염에 맞게 변화시킨 HAQ-S는 건강개념이 추가되어 있는 평가항목이다.

(2) 삶의 질: Ankylosing spondylitis Quality of Life, SF-36, EQ-5D가 많이 사용된다. 강직성척추염 환자뿐만 아니라 거의

모든 류마티스질환의 평가 항목으로 사용된다.

치료반응

강직성척추염 문가 모임은 앞에서 열거한 평가들을 종

합하여 치료에 한 평가를 만들었고, 이 평가항목은 치료

후 효과를 단하는데 리 사용되고 있다 (Figure 1).

2001년 NSAIDs치료 후에 육체 기능, 척추통증, 반

인 환자평가, 염증 등 4항목이 최소 20% 이상 좋아졌는

지 평가를 해 만들어졌고, 이것을 기 로 ASAS20%,

ASAS40%, ASAS 5/6, ASAS partial remission이 만들어져

새로운 약제에 한 평가에 가장 요하게 사용되고 있다.

결 론

지난 수십 년 동안 강직성척추염의 치료방법은 매우 제

한 이었다. 항류마티스 염 치료약제를 사용하는 류마

티스 염과는 달리 강직성 척추염은 비스테로이드성

소염진통제에 의한 증상의 조 과 운동요법이 주된 치료

방법이었다. 그러나 최근 획기 인 치료효과를 보여주는

생물학 제제의 등장으로 조기 진단을 통한 조기 치료가 매

우 요한 이슈로 두되었다. 따라서 고통 받는 많은 환

자들에게 조기 진단과 평가를 히 받을 수 있도록 많은

노력을 기울려야 하겠다.


참고문헌

1. Braun J, van den Berg R, Baraliakos X, Boehm H, Burgos-Vargas R, Collantes-Estevez E, Dagfinrud H, Dijkmans B,

Dougados M, Emery P et al: 2010 update of the ASAS/EULAR recommendations for the management of ankylosing

spondylitis. Ann Rheum Dis 2011, 70(6):896-904.

2. Haslock: Ankylosing spondylitis:management. . rheumatology 3rd ed 2003:1211-1224.

3. Wanders A, Heijde D, Landewe R, Behier JM, Calin A, Olivieri I, Zeidler H, Dougados M: Nonsteroidal antiinflammatory

drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis Rheum

2005, 52(6):1756-1765.

4. Chen J: Is methotrexate effective for the treatment of ankylosing spondylitis? Nat Clin Pract Rheumatol 2007, 3(9):490-491.

5. Haibel H, Rudwaleit M, Braun J, Sieper J: Six months open label trial of leflunomide in active ankylosing spondylitis. Ann

Rheum Dis 2005, 64(1):124-126.

6. Goh L, Samanta A: A systematic MEDLINE analysis of therapeutic approaches in ankylosing spondylitis. Rheumatol Int

2009, 29(10):1123-1135.

7. Zochling J, van der Heijde D, Burgos-Vargas R, Collantes E, Davis JC, Jr., Dijkmans B, Dougados M, Geher P, Inman

RD, Khan MA et al: ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 2006,

65(4):442-452.

8. Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Sieper J, Emery P, Keystone EC, Schiff MH, Mease P

et al: Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2007. Ann Rheum Dis 2007,

66 Suppl 3:iii2-22.

9. Braun J, Baraliakos X, Godolias G, Bohm H: Therapy of ankylosing spondylitis--a review. Part I: Conventional medical

treatment and surgical therapy. Scand J Rheumatol 2005, 34(2):97-108.

10. Song IH, Poddubnyy D: New treatment targets in ankylosing spondylitis and other spondyloarthritides. Curr Opin Rheumatol

2011, 23(4):346-351.

11. Zochling J and Braun J: Assessments in ankylosing spondylitis. Best Practice & Research Clinical Rheumatology 2007,

21(4):699-712.

(2010. 1. 1∼2010. 12. 31)


Poster Presentation

Journal of Rheumatic DiseasesVo l . 2 0 , Sup p l . 1 , May , 20 13 Poster

S191

Monosodium Urate Crystal Enhanced Osteoclastogenesis Through TRAF-6 Signaling Pathway in RAW 264.7 Macrophage Cells

구가톨릭 학교 의과 학 류마티스내과

박기연ㆍ김성규ㆍ이화정ㆍ김주 ㆍ최정윤

Purpose: This study is to investigate action mechanisms by MSU crystals for the regulation of osteoclastogenic activity through

TRAF-6 signal pathways in RAW 264.7 macrophage cells

Methods: We examined the effects of MSU crystals on MAPKs, their signaling cascade genes, and osteoclast differentiation

markers were measured using real-time polymerase chain reaction and western blotting. Effects of TRAF-6 knockdown using

siRNA for TRAF-6 on osteoclastic transcription factors and IL-1β expression were measured by western blotting. We performed

TRAP staining to identify formation of osteoclasts.

Results: MSU crystals induced expressions of IL-1β and MAPK signaling molecules. MSU, in the presence of RANKL, also

resulted in significantly enhanced expressions of osteoclatogenesis related genes. Furthermore, inhibition of TRAF-6 decreased

expressions of IL-1β and its transcription factors such as c-Jun and NFATc1. These results showed that the expression of TRAF-6

signal pathways are active in MSU crystals induced in the presence of RANKL and that these stages can lead to mediated by

the expression of inflammatory osteoclastogenesis.

Conclusions: These results suggest that MSU crystal enhances osteoclast differentiation through TRAF-6 signaling pathway.


S192

Clinical Significance of Caspase-1 Level in Synovial Fluid from Patients with Gout and Other Arthritides

한양 학교 류마티스병원 류마티스내과1, 한양 학교 구리병원 류마티스내과2

손창남1ㆍ방소 2ㆍ김지해1ㆍ최찬범1ㆍ김태환1ㆍ 재범1

Objective: Activation of caspase-1 by NALP3 inflammasomes has been shown to be important in initiating acute gouty arthritis.

The objectives of this study were to measure the levels of caspase-1 in synovial fluid in gout and various arthritides, and to

elucidate the clinical significance of caspase-1 levels in synovial fluid.

Methods: Caspase-1, IL-1β, IL-18, and uric acid were measured in synovial fluid from one hundred and twelve patients with

gout and other arthritides, such as rheumatoid arthritis, osteoarthritis, and spondyloarthropathy.

Results: Caspase-1 in synovial fluid from patients with crystal-induced arthritis, inflammatory arthritis, osteoarthritis, and spondy-

loarthropathy was 35.9±86.7, 49.7±107.7, 2.1±7.0, and 152.6±155.7 pg/mL, respectively. The mean level and the frequency of

high levels (≥125 pg/mL) of caspase-1 in spondyloarthropathy were significantly higher than in the other arthritides including

gout.

Conclusion: Caspase-1 was detectible in the synovial fluid of patients with the various arthritides. Contrary to our hypothesis,

the caspase-1 level in the synovial fluid of patients with gout was not higher than in that of other arthritides. High levels of

caspase-1 may be helpful in differentiating spondyloarthropathy from other arthritides.


S193

MicroRNA-155 as a Proinflammatory Regulator in Acute Gouty Arthritis

Department of Rheumatology, Research Institute of Medical Sciences, Chonnam National University Medical School and Hospital1, Department of Anatomy, Chonnam National University Medical School2,

Department of Laboratory Medicine, Chonnam National University Medical School and Hospital3, National Research Laboratory for Regulation of Bone Metabolism and Disease, Medical Research Center

for Gene Regulation, Chonnam National University Medical School4, Korea

Hye-Mi Jin1, Jung-Ho Choi1, Moon-Ju Kim1, Young-Nan Cho1, Kwang-Il Nam2, Seung-Jung Kee3, Jang Bae Moon

4, Dong-Jin Park

1, Yong-Wook Park

1, Shin-Seok Lee

1, Tae-Jong Kim

1

Introduction: miR-155 is crucial for the proinflammatory activation of human myeloid cells and antigen-driven inflammatory

arthritis. Since, the functional role of miR-155 in gouty arthritis has not been defined. The aim of this study was to examine

the role of mir155 in pathogenesis of gouty arthritis.

Materials and Methods: Samples from fourteen patients with gouty arthritis and ten healthy controls were obtained. MSU

crystals were prepared by recrystallization from uric acid. Total RNA was isolated using the miRNeasy kit (Qiagen). The miScript

Reverse Transcription Kit (Qiagen) was used for cDNA preparation. MiScript primer assay (Qiagen) were used for semi-

quantitative determination of the expression of human miR-155. Human TNF-α and IL-1β in supernatants were measured by

Luminex (Millipore, USA) according to the instructions of the manufacturer. Gout peritonitis mice (Male C57BL/6J) model used

to analyze expressions of mir-155, SHIP-1, and inflammatory cytokines.

Results: The samples from gout patients proved to be highly enriched in mir-155, with levels of expression being 4-fold higher

than those found in PBMC from healthy controls and gout (p＜0.05). Mir-155 was found to be strongly induced by stimulation

of MSU crystals after 24 hours and their expressions gradually decreased. Stimulating with MSU crystals for the indicated times,

and the level of SHIP-1 was found to be gradually decreased in according to over-expression of mir-155. miR-155 promoted

MSU-induced proinflammatory cytokine production. Commensurate with our observations in human synovial monocytes, miR-155

expression was elevated in gout mice model. SHIP1 protein levels were markedly reduced in cells by MSU stimulated, compared

to the control. MSU crystal induced peritonitis mice significantly increased the production of inflammatory cytokines, such as

TNF-α and IL-1β.

Conclusion: Overexpression of miR-155 in SFMC led to down-regulation of SHIP-1 and an increase in the production of proin-

flammatory cytokines.


S194

Quality of Life in Chronic Gouty Arthritis Patients; Comparison Between Patients with or without Tophi

서울 학교 의과 학 내과학교실1, 보건 학원2

김지혜1ㆍ박지원1ㆍ구본승1ㆍ이태진2ㆍ송 욱1ㆍ신기철1

Background: Gouty arthritis is a remittent joint disorder that can affect the basic activities of daily life. Its impact in quality

of life (QOL) can be distressing enough to mimic chronic inflammatory arthritis such as rheumatoid arthritis. On the other hand,

patients occasionally can be symptom-free during the intercritical period of the gouty attack. There have been only few studies

systematically investigating the QOL of chronic gouty arthritis patients.

Materials and Methods: We conducted a survey of gout patients who at least once met the ACR criteria from a single center

(SMG-SNU Boramae Medical Center, from August 2012 to February 2013). The QOL questionnaire was adapted from our re-

cently published study of rheumatoid arthritis patients. Briefly, the survey obtains information regarding patient demographics,

family history of gout, co-morbidities, health-related lifestyles, cost of illness (direct and indirect), and health-related quality of

life (KEQ-5D).

Results: Forty-four male gout patients were enrolled in this study. The mean age was 63.3 (±12.3, S.D.) years old, and the

mean disease duration of gout was 8.1 (±8.0, S.D.) years. Common comorbidities included hypertension, heart disease, and chronic

kidney disease. 27% of patients had chronic tophaceous gout at the time point of the survey. In general, 56.8% of gout patients

stated difficulty in mobility, and 27.3% claimed problems in self-care. However, a significant proportion of patients with chronic

tophaceous gout had impaired functional status compared those without tophi (p=0.0002). Moreover, the percentage of patients

with difficulty in self-care was higher (50%) in chronic tophaceous gout than patients without tophi (18.8%, p=0.058).

Conclusion: Despite that gout could be less debilitating than rheumatoid arthritis once properly controlled, patients with chronic

tophaceous gout are still in dire need of swifter disease control and rehabilitation for a better quality of life.


S195

Elevated Serum Homocysteine Levels in Gouty Patients were Related not with Serum Uric Acid Levels but with Decreased Renal Function

Division of Rheumatology, Department of Internal Medicine, Chung-Ang University Collegd of Medicine, Seoul, Korea

Jin Su Kim, Eun Hye Park, SangTae Choi, Jung-Soo Song

Objectives: Both of hyperhomocysteinemia and goutare related with cardiovascular diseases and metabolic syndrome. However,

there are few reports about the serum homocysteine levels in gouty patients, and theirresults reveal discrepancy. In this study,

we investigated whether or not serum homocysteine levels are elevated in the patients with chronic goutand which factors are

associated with the elevated homocysteine levels.

Methods: This cross-sectional study included 91male patients with chronic gout and 97 age-matched healthy male controls.

The mean ages were 51.19± 15.08and 51.57±17.01 years old, respectively. Serum homocysteine levels were measured by a com-

petitiveimmunoassay using directchemiluminescent. The estimatedglomurular filtration rate (eGFR) was obtainedusing modification

of diet in renal disease formula, thenthe stages of chronic kidney disease (CKD) were classified according to the KDOQI CKD

classification.

Results: The gouty group were not significantly different from the control group in serum uric acid levels (6.15±2.23 mg/dL

vs 5.82±1.22 mg/dL, p=0.224), however, had higher serum homocysteine levels than the control group (13.96±4.05μmol/L vs

12.67±3.52 μmol/L, p=0.021). Serum homocysteine levels showed the positive correlations with serum BUN and Cr levels,

and thenegative correlation with eGFR (r=0.429, p＜0.001; r=0.435, p＜0.001; r=-0.413, p＜0.001, respectively) in the chronic

gouty group. However, serum homocysteine levels are uncorrelated with serum uric acid levels orcholesterolprofiles. The patients

at stages1 or 2 of CKD had significantly lower serum homocysteine levels than the patients at stage 3 of CKD (p＜0.001).

In multiple linear analyses, serum homocysteine level was affected not by the serum uric acid level, but by eGFR (β=-0.385,

p＜0.001).

Conclusions: Serum homocysteine levels were higher in the male patients with chronic gout than in the healthy male controls.

Hyperhomocysteinemia in gouty patients could be related not with serum uric acid levels, but with decreased renal function.


S196

Changes in Bone Mineral Density in Patients with Recent-onset Rheumatoid Arthritis

Division of Rheumatology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Korea

You Jae Kim, Bon San Koo, Yong-Gil Kim, Chang-Keun Lee, Bin Yoo

Background: Generalized bone loss and an increased risk of fractures are regarded as complications in rheumatoid arthritis.

Variable clinical factors, inflammatory activity, and treatment regimens may contribute to the development of bone loss.

Objectives: We evaluated the association between the baseline disease activity and the changes in bone mineral density (BMD)

after 1 year of treatment in a cohort of patients with recently diagnosed active rheumatoid arthritis (RA).

Methods: A total of 106 patients were included in this study. Data on patient’s demographic factors, disease activity score

in 28 joints (DAS28), and anti-rheumatic drugs were obtained. Baseline and 1 year of follow up BMD in proximal femur sites

(i.e., the total femur, femur neck, and trochanter) and lumbar spine were measured with dual energy X-ray absorptiometry.

Regression analyses were performed to determine association between clinical parameters and BMD loss after 1 year.

Results: The mean age of women and men was 50±11 years and 59±7 years, respectively and 54 patients in 92 women were

postmenopausal status. The mean baseline DAS28 was 5.4±1.2 (range; 2.6∼8.6) and 30 (28.3%) patients were diagnosed as

osteoporosis at baseline. After 1 year of treatment, the mean annualized rates of bone loss in the total femur, femur neck, tro-

chanter, and L-spine were －1.41%/yr, －1.31%/yr, －2.07%/yr, and －0.78%/yr, respectively. Age, smoking, menopause, and

high DAS28 were associated with prominent BMD loss in femur neck. Higher cumulative dose of corticosteroids was associated

with significant bone loss in the spine and femur. The use of bisphosphonate had no significant protected effect against BMD

loss in one year of treatment.

Conclusions: High baseline disease activity and increased dose of steroids are significantly associated with accelerated BMD

loss in patients with active RA. Suppression of inflammation at the initial treatment might reduce the bone loss and limited

use of steroids can be essential for bone preservation.


S197

The Prevalence of and Risk Factors for Osteoporosis in Patients with Rheumatoid Arthritis in South Korea

Inje University Ilsan Paik Hospital1, Hanyang University Hospital for Rheumatic Diseases2, Hanyang University Guri Hospital3, Catholic University of Daegu School of Medicine4, Kyung Hee University Hospital5, Ewha Womans University Mokdong Hospital6, Korea

Joo-Hyun Lee1, Yoon-Kyoung Sung2, Jeeseon Shim2, Chan-Bum Choi2, Soo-Kyung Cho2, So-Young Bang3, Jung-Yoon Choe4, Seung-Jae Hong5, Jae-Bum Jun2, Tae-Hwan Kim2,

Jisoo Lee6, Hye-Soon Lee

3, Dae-Hyun Yoo

2, Bo Young Yoon

1, Sang-Cheol Bae

2

Objectives: This study was to investigate the prevalence of and the risk factors for osteoporosis in RA patients using the KORean

Observational study Network for Arthritis (KORONA) database, a nationally representative Korean RA specific cohort.

Methods: Among patients recruited for KORONA between September 2009 and December 2011, only postmenopausal women

and men ＞50 years RA patients were enrolled in this study. Also, the data of RA patients (n=1,454) measured bone mineral

density (BMD) within 1 year at KORONA enrollment was analyzed in this study. BMD measurement rates were analyzed for

enrolled RA patients, and the prevalence of osteoporosis in the study patients was calculated for age and gender subgroups.

multiple linear regression analyses were used to explore the association between osteoporosis and the demographic and dis-

ease-related risk factors.

Results: Total of 3,531 patients (postmenopausal women and men age more than 50) were enrolled for the study. Among them,

1,454 patients (41.2%) had BMD evaluation done within 1 year from the study enrollment. 653 (44.9%), 651 (44.8%), and 150

(10.3%) patients belonged to the osteoporosis, osteopenia, and normal groups, respectively. The demographic and disease-related

variables were statistically tested in a multivariate regression model as independent predictors of osteoporosis in patients with

RA. As a result, older age (＞70 yrs) (OR=2.05, 95% CI: 1.41∼2.99), lower body weight (OR=0.50, 95% CI: 0.36∼0.69),

longer disease duration (＞10 yrs) (OR=1.73, 95% CI: 1.33∼2.24) and higher HAQ score (OR=1.72, 95% CI: 1.39∼2.17) were

analyzed as statistically significant independent associated with osteoporosis.

Conclusion: Osteoporosis in RA patients was highly prevalent in Korea. Especially, osteoporosis in women had significantly

higher than that in men. However, over half of the patients with RA who participated in the KORONA study had not had a

BMD evaluation at enrollment. As a result, the assessment of BMD and screening of osteoporosis should be considered for

RA patients, particularly for high-risk groups.


S198

Are Glucocorticoid-Induced Osteoporosis Recommendations Sufficient to Determine Anti-Osteoporotic Treatment

for Patients with Rheumatoid Arthritis?

Department of Internal Medicine, Inje University Ilsan Paik Hospital1, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases2, Korea

Joo-Hyun Lee1, Soo-Kyung Cho2, Minkyung Han2, Dam Kim2, Sang-Cheol Bae2, Yoon-Kyoung Sung2

Background/Aims: We compared two guidelines to identify candidates for anti-osteoporotic treatment for rheumatoid arthritis

(RA) patients and investigated the impact of screening for vertebral fractures (VFs) on deciding to implement anti-osteoporotic

treatment.

Methods: We applied the Glucocorticoid-Induced Osteoporosis (GIOP) recommendations and the National Osteoporosis

Foundation (NOF) guidelines to RA patients and examined the agreement between two guidelines for identifying candidates for

anti-osteoporotic treatment. Also, we analyzed the impact of screening VFs on determining treatment of osteoporosis in RA

patients.

Results: The 57 patients taking glucocorticoids were classified into high-risk (n=23), medium-risk (n=16), and low-risk (n=18)

groups according to GIOP recommendations. Based on the NOF guidelines, 36 of 57 patients were candidates for anti-osteoporotic

treatment and the agreement between two guidelines was high (kappa=0.764). Two of the 18 patients in the low-risk group and

19 of 43 patients not eligible for GIOP recommendations were classified as candidates for anti-osteoporotic treatment by NOF

guidelines.

Conclusion: In determining anti-osteoporotic treatment for RA patients, only using GIOP recommendations is not sufficient.

The application of NOF guidelines in patients not eligible for or classified as low risk group by GIOP recommendations and

screening for VFs might be helpful to decide anti-osteoporotic treatment in RA patients.


S199

생물학 제재와 NSAIDs를 사용하는 강직성 척추염 환자에서 골 도의 변화에 한 비교 연구

동아 학교 의과 학 내과학교실 류마티스내과

이상엽ㆍ임상우ㆍ이성원ㆍ정원태

배경: 강직성 척추염에서는 골 도가 감소하여 골다공증이 생기는 데, 이는 만성 인 염증에 의해서 정상인보다 골 도

의 감소가 비교 이른 시기부터 나타나고, 골다공증에 의한 척추 골 이 정상군에 비해 더 많이 발생한다고 알려져

있다.이에 본 연구에서는 최근 강직성 척추염 치료제로 많이 사용 하는 생물학 제재와 기존의 NSAIDs를 동시에 사용하

는 강직성 척추염 환자군과 NSAIDs만을 사용하는 군간에 골 도의 감소여부, 각 부 별 골 도의 차이 등을 조사하고,

ESR CRP 등의 염증 련 수치에 따라 각 군 간의 요추부와 퇴부의 골 도의 차이를 조사하 다.

상 방법: 총 80명의 환자를 모집하여 2010년과 2012년에 걸쳐 2번의 골 도 검사를 시행하 으며 80명의 한자 에서

16명이 탈락하여, 총 64명을 상으로 요추부와 양측의 퇴부에 한 골 도 검사를 시행하 으며 동시에 체질량 지수,

ESR과 CRP를 측정하 다.

결과: 64명의 환자 에서 16명의 환자는 생물학 제재와 NSAIDs를 동시에 사용하 고, 48명의 환자는 NSAIDs만을

사용하 다.처음 시행한 골 도 검사에서 생물학 제재와 NSADIs를 동시에 사용한 16명 환자군의 요추부 골 도 평균

은 0.4 g/cm2, 우측 퇴부는 －0.7 g/cm2, 좌측 퇴부는 －0.7 g/cm2 고, NSAID만 사용한 48명 환자군의 요추부 골 도

평균은 0.22 g/cm2, 우측 퇴부는 －0.4 g/cm2, 좌측 퇴부는 －0.38 g/cm2 다. 2년 후 다시 시행한 골 도의 변화의

평균은 16명 환자군의 요추부 골 도는 0.61 g/cm2, 우측 퇴부는 －0.6 g/cm2, 좌측 퇴부는 －0.7 g/cm2 고, 48명의

환자군의 요추부 골 도는 0.31 g/cm2, 우측 퇴부 －0.38 g/cm2, 좌측 퇴부는 －0.3 g/cm2 다. 2년간의 골 도 변화의

평균은 생물학 제재와 NSAIDs를 동시에 사용한 16명의 환자에서는 요추부 골 도 0.21 g/cm2, 우측 퇴부 0.08 g/cm

2,

좌측 퇴부 0.05 g/cm2 고, NSAIDs만을 사용한 48명의 환자는 요추부 골 도 변화 평균은 0.09 g/cm2, 우측 퇴부는

0.02 g/cm2, 좌측 퇴부는 0.08 g/cm2 다. 생물학 제재와 NSAIDs를 동시에 사용한 군에서 NSAIDs만을 사용한군에

비해 골 도의 증가 변화가 높았지만 통계 으로는 유의하지 못했다. BMI, SEX, ESR, CRP 변화 에서 CRP가 NSAIDs를

사용한 군의 요추부 골 도 변화와 통계 으로 유의하 다.

결론: 2년간 골 도 변화 연구에서 생물학 제재와 NSAIDs를 동시에 사용한 군에서 유의한 골 도 증가를 보 다.


S200

Coenzyme Q10 Ameliorates Pain and Cartilage Degradation in a Rat Model of Osteoarthritis by Regulating Nitric Oxide

and Inflammatory Cytokines

가톨릭 학교 내과학교실 류마티스분과1, 가톨릭 학교 류마티스 연구센터2, 한림 학교 내과학교실 류마티스분과3

이주하1ㆍ홍연식1ㆍ정정희2ㆍ양은지2ㆍ 주연2ㆍ박미경2ㆍ정 옥3ㆍ민 기1ㆍ조미라2ㆍ박성환1

Objective: To investigate the effect of CoenzymeQ10 (CoQ10) on pain severity and cartilage degeneration in an experimental

model of rat osteoarthritis (OA).

Materials and Methods: OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee.

Oral administration of CoQ10 was initiated on day 4 of MIA injection. Pain severity was assessed by measuring secondary tactile

allodynia using the von Frey assessment test. The degree of cartilage degradation was determined by measuring cartilage thickness

and the amount of proteoglycan. The mankin scoring system was also used. Expressions of matrix metalloproteinase-13 (MMP-13),

interleukin-1β (IL-1β), IL-6, IL-15, inducible nitric oxide synthase (iNOS), nitrotyrosine and receptor for advanced glycation

end products (RAGE) were analyzed using immunohistochemistry.

Results: Treatment with CoQ10 demonstrated an antinociceptive effect in the OA animal model. The reduction in secondary

tactile allodynia was shown by an increased pain withdrawal latency and pain withdrawal threshold. CoQ10 also attenuated carti-

lage degeneration in the osteoarthtritic joints. MMP-13, IL-1β, IL-6, IL-15, iNOS, nitrotyrosine and RAGE expressions were

upregulated in OA joints and significantly reduced with CoQ10 treatment.

Conclusion: CoQ10 exerts a therapeutic effect on OA via pain suppression and cartilage degeneration by inhibiting inflammatory

mediators, which play a vital role in OA pathogenesis.


S201

Clinical Courses and Predictors of Outcomes in Patients with Monoarthritis: a Retrospective Study of 171 Cases

Department of Medicine, Samsung Medical Center1, Kangbuk Samsung Hospital2, Sungkyunkwan University School of Medicine, Korea

Hyemin Jeong1, In Young Kim

1, Eun-Jung Park

1, Jiwon Hwang

1, Hyungjin Kim

1,

Joong Kyong Ahn2, Jaejoon Lee1, Eun-Mi Koh1, Hoon-Suk Cha1

Objectives: To evaluate the clinical courses and outcomes of patients with monoarthritis and to investigate the predictive factors

of clinical outcomes.

Methods: A retrospective analysis was performed of 171 patients with chronic monoarthritis at a single tertiary hospital between

January 2001 and January 2011. Baseline characteristics, radiographic findings and the clinical course were reviewed.

Results: The most commonly involved joints were the knees (24.0%), followed by the wrists (22.8%) and ankles (18.7%).

A final diagnosis was established in 74 (43.3%) patients. Of these, 31 (41.9%) patients were diagnosed with rheumatoid arthritis

(RA), 23 (31.1%) patients with peripheral spondyloarthritis (SpA), and 19 (25.7%) patients with Behçet’s disease (BD). Among

108 patients who were initially undiagnosed, 85 (78.7%) patients remained with undiagnosed monoarthritis, with relatively shorter

symptom durations and requiring less treatment. The initially involved joint was a predictive factor for the final diagnosis: the

wrist joint for RA (OR 11.58, p＜0.001), the ankle joint for SpA (OR 6.19, p＜0.001), and the knee joint for BD (OR 3.43,

p=0.014). Bony erosion at baseline was associated with progression to oligo- or polyarthritis (OR 2.88, p=0.030) and with radio-

graphic progression.

Conclusions: In patients presenting with monoarthritis, a final diagnosis was established in less than half of the patients, and

a majority of undiagnosed patients showed benign clinical courses. The initially involved joint and the presence of erosion at

baseline were predictors of the final diagnosis and of clinical outcomes.


S202

HMGB1 Regulates Hypoxia-inducible Factor 1α Expression and Function in Synovial Fibroblasts from Patients with Rheumatoid Arthritis

부산 학교 의학 문 학원 약리학교실, 허 조직재생연구센터

박소연ㆍ김혜 ㆍ홍기환ㆍ김치

Background: High mobility group box chromosomal protein 1 (HMGB1) is a nuclear DNA binding protein that is secreted

into extracellular medium by cellular activation and proinflammatory response, and promotes inflammation. HMGB1 is known

as ligand for TLR4 that produces TNF-α and IL-8. Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor

which is composed of an alpha and beta subunit. HIF-1 has been reported as regulator of angiogenesis in rheumatoid arthritis

(RA).

Objectives: We investigated the role and molecular mechanism of HMGB1 in the expression and function of HIF-1α in synovial

fibroblasts from patients with RA.

Methods: HIF-1 activity and VEGF expression were measured by ELISA. Signaling and molecular events were analyzed by

immunoblotting.

Results: The expression of extracellular HMGB1 was increased in synovium of RA patients than OA patients. Treatment of

RA synovial fibroblasts with HMGB1 increased HIF-1α expression and HIF-1 activity. HMGB1 mediated production of VEGF

was dependent upon HIF-1. When TLR4 was blocked by TLR4 siRNA or anti-TLR4 antibody, HIF-1α didn’t be increased,

leading to abolish the increase in VEGF production.

Conclusions: Our results suggest that HMGB1stimulation of HIF-1α expression and activity results in VEGF expression that

is dependent upon TLR4.


S203

Reciprocal Activation of CD4+T Cells and Synovial Fibroblasts by Stromal Cell-derived Factor (SDF)-1 Promotes RANKL Expression

and Osteoclastogenesis in Rheumatoid Arthritis

건국 학교 의학원문 학원 내과학교실 류마티스내과1, 가톨릭 학교 류마티스연구센터2

김해림1ㆍ김경운

1ㆍ김보미

1ㆍ조미라

2ㆍ이상헌

1

Objective: Stromal cell-derived factor (SDF)-1 is a chemokine that is involved in the bone destructive process in rheumatoid

arthritis (RA) and bony metastasis in malignancy. This study was performed to determine the role and mechanism of action

of SDF-1 on osteoclastogenesis in RA.

Methods: SDF-1 and receptor activator of nuclear factor kB ligand (RANKL) expression in RA synovial tissues were determined

by confocal microscopy and ELISA. After RA fibroblast-like synoviocytes (FLS) and CD4+ T cells were treated with SDF-1,

RANKL expression was assayed by real-time PCR. Osteoclastogenesis was assessed by counting tartrate-resistant acid phosphatase

(TRAP)-positive multinucleated cells after isolated CD14+ monocytes were cultured with SDF-1 in the presence of anti-cytokine

antibodies and intracellular signal inhibitors. Osteoclastogenesis was also determined after co-culture of monocytes with SDF-1–pretreated FLS and CD4+ T cells.

Results: RANKL concentration was correlated with SDF-1 concentration in RA synovial fluid. SDF-1 stimulated RANKL ex-

pression in RA FLS and CD4+ T cells, and SDF-1–induced RANKL expression was decreased with blockage of TNF-alpha.

When peripheral blood monocytes were cultured with SDF-1, osteoclasts were differentiated in the absence of RANKL. In addi-

tion, monocytes differentiated into osteoclasts when co-cultured with SDF-1–pretreated RA FLS or CD4+T cells in the absence

of RANKL and the osteoclastogenesis was decreased by blocking TNF-alpha.

Conclusion: SDF-1 attenuated osteoclastogenesis by upregulating RANKL expression of RA FLS and CD4+ T cells, which

was mediated by TNF-alpha. The axis of SDF-1 and RANKL is a potential therapeutic target for RA-associated bone destruction.


S204

Caspase-5 Inhibitor 처치에 따른 류마티스 염 활막세포에서의 활막세포 증식의 억제 염증매개인자 감소 효과


권용진ㆍ김태연ㆍ이상원ㆍ송정식ㆍ박용범ㆍ이수곤ㆍ박민찬

배경: Caspase는 cysteine protease의 일종으로 apoptosis 과정에서 요한 역할을 한다. 그러나, caspase-5는 염증반응에 주로

여하는 것으로 밝 졌는데 cytokine의 생성, 세포의 분화와 증식 NF-κB의 활성화를 유발하는 것으로 알려졌다.

NF-κB는 류마티스 염의 발병에 요한 역할을 하므로 caspase-5 inhibitor가 류마티스 염에서도 염증을 억제할

수 있을 것으로 생각되나 아직까지 류마티스 염에서 caspase-5 inhibitor의 항염증작용에 해서 정확히 밝 진 바가

없다. 본 연구에서는 류마티스 염에 있어서 caspase-5 inhibitor의 항염증작용 이의 작용기 을 알아보고자 하 다.

방법: 류마티스 염 환자와 골 염 환자의 활막조직으로부터 섬유모세포양 활막세포를 분리 배양하여 IL-1β (2

ng/mL), TNF-α (20 ng/mL) 는 LPS (1,000 ng/mL)를 처리한 군과 처리하지 않은 군으로 나 어 caspase-5의 mRNA 발

정도를 real-time PCR을 통해 정량분석하 다. Caspase-5 inhibitor인 Z-WEHD-fmk를 처리한 후 real-time PCR을 통해 IL-1

β, IL-6, IL-18, COX-2, MMP-9과 CCL2의 mRNA 발 감소 정도를 확인하 고, Z-WEHD-fmk처치에 따른 활막세포의

증식 억제여부를 MTT assay를 통해 측정하 다. 한 nuclear extracts로부터 EMSA를 시행하여 식세포의 표 인 염증

반응 신호 달체계인 NF-κB의 억제 여부를 확인하 다.

결과: 골 염 환자에 비해 류마티스 염 환자의 활막세포에서 caspase-5의 mRNA 발 정도가 증가되어 있었고 IL-1

β, TNF-α 는 LPS를 처리한 경우 류마티스 염 환자의 활막세포에서 caspase-5의 mRNA의 발 이 더욱 증가하 다.

Z-WEHD-fmk를 처리함에 따라 IL-1β, IL-6, IL-18, COX-2, MMP-9과 CCL2의 mRNA 발 이 감소하 고 섬유모세포양

활막세포의 증식이 억제되었다. 한 Z-WEHD-fmk를 처리한 섬유모세포양 활막세포에서 NF-κB가 억제됨을 확인하 다.

결론: Caspase-5는 류마티스 염 환자의 섬유모세포양 활막세포에서 발 이 증가되어 있으며 억제할 경우 다양한 염증

매개물질의 생성이 감소되며 이러한 반응은 NF-κB활성 억제에 의해 유발됨을 찰하 다. 본 연구를 통하여 caspase-5가

류마티스 염의 병인에 여함을 확인하 으며 류마티스 염의 치료에 있어서 새로운 치료방침을 제공할 수 있을

것으로 생각한다.


S205

Rebamipide Suppresses Collagen-induced Arthritis Through Reciprocal Regulation of Th17/Treg Differentiation and Heme Oxygenase-1 Induction

Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea1, Rheumatism Research Center, Catholic Institutes of Medical Science, The Catholic University of Korea2, Korea

Su-Jin Moon1, Jin-Sil Park

2, Mi-La Cho

2, Jun-Ki Min

1

Aims: Rebamipide, a gastroprotective agent, has been asserted to have the ability to scavenge reactive oxygen radicals. Increased

oxidative stress is implicated in the pathogenesis of rheumatoid arthritis (RA). In this study, we investigated the impact of re-

bamipide on the development of arthritis and its pathophysiologic mechanisms by which rebamipide attenuated arthritis severity

in a murine model of RA (collagen-induced arthritis [CIA] in DBA/1J mice).

Results: We showed that treatment with rebamipide markedly suppressed the severity of histological inflammation and cartilage

destruction in a dose-dependent manner. The joints isolated from rebamipide-treated arthritis mice showed decreased expression

of oxidative stress marker (nitrotyrosine). Rebamipide-treated mice showed lower circulating levels of type II-collagen specific

total IgG, IgG1 and IgG2. IL-17-producing CD4+ T cells (Th17) in spleen were decreased in rebamipide-treated animals.

Conversely, significantly increased number of CD4+CD25+Foxp3+ regulatory T cells (Treg) in spleens was observed in re-

bamipide-treated mice. In vitro, rebamipide inhibited Th17 differentiation through STAT3/RORγt, and it induced Treg through

Foxp3 induction. In vitro, rebamipide increased Nrf (NF-E2-related factor 2) nuclear activity in murine CD4+ T cells and murine

T cell line (LBRM-33). In spleen of rebamipide-treated mice, the expression of heme oxygenase-1 (HO-1) was markedly increased.

Innovation: Rebamipide exhibited anti-arthritis property through reciprocal regulation of Th17 and Treg and also showed anti-

oxidant activity by Nrf2/HO-1 pathway activation.

Conclusion: The inhibitory effects of rebamipide on joint inflammation are associated with the restoration of Th17/Treg balance

and Nrf2/HO-1 antioxidant pathway activation.


S206

Kaempferol Inhibitis IL-1β-induced Proliferation and Production of MMPs, COX-2 and PGE2 by Rheumatoid Synovial Fibroblasts

Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine of Chonbuk National University Hospital-Chonbuk National University

Pil-Hun Song, Yun-Jung Choi, Ha-Yong Yoon, Eun-Gyeong Lee, Myung-Soon Sung, Won Seok Lee, Wan-Hee Yoo

Background: Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease characterized by chronic synovitis with

subsequent articular bone and cartilage destruction. Chronic inflammation with hyperplasia of synovial lining cells including syno-

vial fibroblast is histologic characteristics of RA joint. Rheumatoid synovial fibroblast (RASF) plays a key role in the pathogenesis

of RA synovitis. Inflammatory cytokines, matrix-metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2) from RASFs are

involved in destruction of both articular bone and cartilage. Kaempferol has been reported to inhibit nitric oxide synthase and

cyclooxygenase enzymes in animal model. whether kaempferol modulates the cyclooxygenase pathway via inhibition of nitric

oxide production, which in turn contributes to its anti-inflammatory activity.

Objectives: The present study was designed to investigate the effects of kaempferol on the interleukin-1β (IL-1β)-induced

proliferation of rheumatoid synovial fibroblasts (RASFs) and production of matrix metalloproteinases (MMPs), cyclooxygenase

(COX) and prostaglandin E2 (PGE2) by RASFs.

Materials and Methods: The proliferation of RASFs was evaluated with CCK-8 reagent in the presence of IL-1β with/without

kaempferol. The expression of MMPs, TIMP-1, COXs, PGE2 and intracellular MAPK signalings, including p-ERK, p-p38, p-JNK

and NF-kB were examined by immunoblotting or semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR)

and ELISA in conditions as described above.

Results: Kaempferol inhibits unstimualted and IL-1β-induced proliferation of RASFs and MMP-1, 3, COX-2 mRNA and protein

expression, PGE2 production induced by IL-1β. Kaempferol also inhibits the phosphorylation of ERK-1/2, p38, JNK and activa-

tion of NF-kB by IL-1β.

Conclusion: These results indicate that kaempferol inhibits synovial fibroblasts proliferation and MMPs, COX-2, PGE2 pro-

duction which involved joint destruction in RA and suggest that it might be a new therapeutic agent for management of RA.


S207

Serum IL-34 Level is Associated with Radiographic Progression in Early Rheumatoid Arthritis

분당서울 학교병원

장성혜ㆍ최병용ㆍ조 정ㆍ강은하ㆍ이윤종

Objective: IL-34 is a recently identified cytokine that can induce human osteoclast differentiation and its expression was reported

to be increased in rheumatoid arthritis (RA) synovium. We measured the circulating levels of IL-34 and investigated its clinical

implications in RA patients.

Method: Peripheral blood samples were obtained from patients with RA (n=100) or ankylosing spondylitis (AS, n=36), and

59 healthy controls. Synovial fluid (SF) samples were from patients with RA (n=18) and osteoarthritis (OA, n=19). The levels

of IL-34 were determined by enzyme-linked immunosorbent assay. Clinical variables including the disease duration, smoking

status, laboratory data, and current medications were collected. RA disease activity was evaluated by Disease Activity Score

28 (DAS28-ESR) and radiologic damage was assessed by the modified total Sharp score.

Results: Serum IL-34 levels were significantly higher in patients with RA (p＜0.001) or AS (p＜0.01) than those in controls

and SF IL-34 levels were significantly elevated in RA patients when compared to those of OA patients (p＜0.0001). In RA

patients, higher serum IL-34 levels were significantly associated with rheumatoid factor (RF) positivity (p=0.01), current smoking

history (p＜0.05), higher ESR (≥ 20 mm/h versus＜20 mm/h, p＜0.001) levels, and early disease (disease duration ≤ 6 months

versus ≥ 5 years). Circulating IL-34 levels tended to be higher in RA patients with radiographic progression (change in SHS

total scores ≥ 1 unit) than in those without progression (p=0.053). Acording to the disease duration, serum IL-34 levels were

significantly elevated in early RA with radiographic progression compared to those without progression (p＜0.05).

Conclusion: The present study showed that serum IL-34 levels are increased in RA patients and are associated with radiographic

damage status or progression in early RA. Further studies are required to verify the association between serum IL-34 levels

and radiologic outcome in early RA patients.


S208

Increased Level of IL-34 in Serum and Synovial Fluid is Associated with Rheumatoid Factor and Anti-cyclic Citrullinated Peptide

Antibody Titers in Patients with Rheumatoid Arthritis

가톨릭 학교 의과 학 내과학교실 류마티스내과

문수진ㆍ홍연식ㆍ주지 ㆍ박성환ㆍ민 기

Objective: Interleukin-34 (IL-34) is a recently discovered cytokine that binds macrophage colony-stimulating factor (M-CSF)

receptor. Rheumatoid arthritis (RA) is characterized by increased osteoclastogenesis. To identify the significance of IL-34 in RA,

the IL-34 concentration was measured in serum and synovial fluid (SF).

Methods: IL-34 concentration were measured in serum from RA (n=113), osteoarthritis (OA) (n=56), and controls (n=36), and

in SF isolated from RA (n=36) or OA (n=24) patients. Correlations between serum IL-34 level and clinical features were assessed

in RA. The levels of IL-1β, IL-6, IL-17α, interferon-γ-induced protein 10, receptor activator of nuclear factor κB (RANKL),

and dickkopf-1 were also measured.

Results: RA patients had a higher mean serum level of IL-34 than did OA and controls (188.0±550.3, 36.6±38.0, and 49.1±78.5

pg/ml, respectively). Similarly, SF IL-34 concentration was also higher in RA than in OA. IL-34 levels were positively associated

with IL-6 levels in serum from RA and OA patients. SF IL-34 concentration correlated significantly with IL-6 and RANKL

levels only in RA. Interestingly, serum IL-34 level in RA patients with osteoporosis was higher than those without osteoporosis.

IL-34 level in serum of RA patients were correlated significantly with rheumatoid factor (RF) and anti-cyclic citrullinated peptide

(anti-CCP) antibody titers (r=0.282 and 0.491, respectively).

Conclusions: Circulating IL-34 level in RA correlated with systemic bone loss and autoantibody production. Further inves-

tigations of localized and systemic effects of IL-34 are warranted to elucidate RA pathogenesis.


S209

Plasma Leucine-rich alpha-2 Glycoprotein is a Useful Disease Activity Biomarker in Rheumatoid Arthritis

연세 학교 의과 학 내과학교실 류마티스내과1, 앙 학교 의과 학 내과학교실 류마티스내과2, 부산의료원 류마티스내과3

하유정1ㆍ최상태

2ㆍ송정수

2ㆍ강은진

3ㆍ이상원

1ㆍ박용범

1ㆍ이수곤

1

Backgrounds and Objectives: Leucine-rich α2-glycoprotein (LRG) is a plasma protein which contains leucine-rich repeats

(LRRs). Though physiological functions of LRG have not been clarified yet, it has been reported that LRG could be a marker

of granulocytic differentiation and its expression was up-regulated during neutrophil differentiation. LRG could show a significant

increase in some inflammatory conditions, such as ulcerative colitis. This study aimed to investigate whether the plasma LRG

level is elevated in patients with RA and its correlation with disease activity and other parameters.

Methods: Our study included 69 patients with RA and 48 age- and sex- matched healthy controls. We assessed the clinical

characteristics and laboratory parameters including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and disease

activity score 28 (DAS28). Plasma concentrations of tumor necrosis factor-α (TNF-α) and LRG were determined by en-

zyme-linked immunosorbent assay (ELISA).

Results: Plasma LRG concentrations were significantly elevated in RA patients compared with healthy control (30.8±14.4 ng/mL

vs 22.2±6.1 ng/mL, p＜0.001). In patients with RA, plasma LRG levels were found to be correlated with DAS28, ESR, and

CRP (γ=0.671, p＜0.001; γ=0.612, p＜0.001; and γ=0.601, p＜0.001, respectively), but not with plasma TNF-α levels. Plasma

LRG levels in patients with an active disease status (DAS28≥2.6) were significantly higher than in patients with a remission

status (DAS28＜2.6) (36.45±14.36 ng/mL vs 24.63±8.81 ng/mL, p＜0.001).

Conclusion: Patients with RA had higher plasma LRG levels than healthy subjects, and plasma LRG levels were well correlated

with disease activity measures. Our findings suggest that plasma LRG could play a role in the inflammatory process independently

of the TNF- α, and that it may be a novel biomarker for reflecting inflammatory activity in RA patients.


S210

Relation of Rheumatoid Factor and Anti-cyclic Citrullinated Peptide Antibody with Disease Activity in Rheumatoid Arthritis:

Cross-sectional Study

Division of Rheumatology, Department of Internal Medicine, Arthritis & Autoimmunity Research Center1, Department of Preventive Medicine, Catholic University of Daegu School of Medicine2, Daegu, Korea

Seong-Kyu Kim1, Jisuk Bae2, Hwajeong Lee1, Jung-Yoon Choe1

Objective: To identify the potential role of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP)

as markers of disease activity and remission status in patients with rheumatoid arthritis (RA).

Methods: A total of 385 patients with RA were consecutively enrolled in this cross-sectional study. Disease activity indices

included disease activity score 28 (DAS28), the simplified disease activity index (SDAI), and the clinical disease activity index

(CDAI). Levels of anti-cyclic citrullinated peptide (anti-CCP) antibody and rheumatoid factor (RF) were measured. Serum titers

of RF and anti-CCP antibody were transformed into incremental levels (/100 units) and log-transformed levels. Remission of

RA activity was defined as the achievement of ≤2.6 in a DAS28 score at study enrollment.

Results: Patients not in remission (n=286) had higher log-transformed RF levels than those in remission (n=99, p=0.02). Serum

RF titers and log-transformed RF levels were closely associated with DAS28 score (p=0.003 and p=0.001). The log-transformed

RF level was associated with an increased risk of non-remission of RA (OR=1.32, 95% CI 1.04∼1.67). Higher log-transformed

RF levels and incremental RF values were associated with an increased risk of non-remission in RA patients with shorter disease

duration (＜10 years) using steroids (OR=1.51, 95% CI 1.15∼1.99 and OR=2.06, 95% CI 1.22∼3.48, respectively).

Conclusions: This study reveals that log-transformed RF levels might be associated with remission status in RA patients, espe-

cially those with a shorter disease duration who are taking steroids.


S211

Effects of Early Diagnosis on Disease Activity and Functional Disability in Rheumatoid Arthritis: Cross-sectional Study of the KORONA Cohort Database

Hanyang University Hospital for Rheumatic Diseases1, Clinical Research Center for Rheumatoid Arthritis (CRCRA)2, Inje University Ilsan Paik Hospital3, Sungkyunkwan University School of Medicine, Samsung Medical Center4,

Hanyang University Guri Hospital5, Jeju National University Hospital6, Ewha Womans University Mokdong Hospital7, Catholic University of Daegu School of Medicine8

, Konkuk University Medical Center9, Chungnam National

University Hospital10, Kyung Hee University Hospital

11, Chonnam National University Hospital

12,

Dong-A University Hospital13, Hallym University Kangnam Sacred Heart Hospital

14, Korea

Dam Kim1, Chan-Bum Choi1,2, Jiyoung Lee2, Yoon-Kyoung Sung1,2, Soo-Kyung Cho1,2, Bo Young Yoon3, Dae-Hyun Yoo1, Eunmi Koh4, Hoon-Suk Cha4, Hye-Soon Lee5, Jae-Bum Jun1,

Jaejoon Lee4, Jinseok Kim

6, Jisoo Lee

7, Jung-Yoon Choe

8, Sang-Heon Lee

9, Seong-Kyu Kim

8,

Seung-Cheol Shim10, Seung-Jae Hong11, Shin-Seok Lee12, So-Young Bang5, Sung Won Lee13, Tae-Hwan Kim1, Tae-Jong Kim12, Won Tae Chung13, Young Ok Jung14, Sang-Cheol Bae1,2

Objectives: To determine whether early diagnosis and treatment have long-term benefits for disease activity and functional

disability in patients with RA enrolled in the KORean Observational study Network for Arthritis (KORONA).

Methods: A total of 4540 rheumatoid arthritis patients completed questionnaires to establish their demographic profile, medical

history, disease-specific outcomes, and RA-related information. We defined early and delayed RA diagnoses as lag-times of shorter

than and at least 1 year. Disease activity was measured with the Disease Activity Score employing 28 joints (DAS28)–ESR,

and it was dichotomized using a score of 2.6. Functional disability was measured with the Korean Health Assessment

Questionnaire–Disability Index (KHAQ-DI), and was dichotomized using a score of 1. We used the chi-square test, t-test, crude

and multiadjusted models to identify the impacts of early diagnosis on disease activity and functional disability.

Results: In crude and multiadjusted models, early diagnosis was not associated with a higher remission rate (OR 1.10, CI 0.94∼

1.28 in crude model, OR 1.05, CI 0.83∼1.32 in multiadjusted model). We performed subgroup analysis according to disease

duration; there was no association between early diagnosis and remission rate. Early diagnosis was associated with functional

disability in crude model (OR 0.79, CI 0.68∼0.91) but not in multiadjusted model (OR 0.85, CI 0.72∼1.002). Functional dis-

ability was associated with a higher DAS28-ESR, female gender, advanced age, longer disease duration, and delayed diagnosis.

In subgroup analysis according to disease duration and disease activity, early diagnosis was independently associated with func-

tional disability for a shorter disease duration (OR 0.78, CI 0.63∼0.96 in disease duration ＜10 years) and the presence of

moderate-to-severe disease activity (OR 0.83, CI 0.69∼0.99 in DAS28-ESR ≥3.2).

Conclusions: Early diagnosis is associated with functional disability especially with a disease duration of less than 10 years

and the presence of moderate-to-severe disease activity.


S212

Musculoskeletal Ultrasonography of Distal Lower Extremities in Rheumatoid Arthritis; A Pilot Study of 50 Patients

서울 학교 의과 학 내과학교실1, 서울조인트내과2

구본승1ㆍ이정찬2ㆍ신기철1

Background: In daily clinical practice, a thorough assessment of ankles and feet for rheumatoid arthritis (RA) patients can

be rather limited. Furthermore, DAS28 does not incorporate joint evaluation of ankles and feet. The aim of this cross-sectional

pilot study was to identify common ultrasonographic findings in distal lower extremities of RA patients seen in daily practice.

Methods and Materials: RA patients meeting the 2010 ACR criteria were recruited consecutively from a single secondary

medical center (SMG-SNU Boramae Medical Center, from October 2012 to February 2013). Ultrasonography (US) of ankles

and feet were obtained to assess erosions, joint effusions, synovial hypertrophy, and tenosynovitis. We also acquired clinical

and laboratory information to assess DAS28, DAS44, RAPID3, as well as plain radiography of the ankles and feet.

Results: Fifty patients were enrolled in this study (male:female=7:43). The mean age of the patients was 59.1 years, and the

mean duration of disease was 63.0 months. Mean DAS28 was 4.02, and mean DAS44 was 2.73. Upon joint exam, 66% of

total patients had at least 1 swollen and/or tender joint in the ankles or feet. When using US, bony erosion was most commonly

found at the 5th metatarsophalangeal joint. Joint effusion was mainly detected at the tibiotalar joint. Of note, tenosynovitis on

US was well appreciated in the extensor digitorum longus tendon (35/50 patients), and extensor hallucis longus tendon (32/50

patients); more frequent than ankle joint involvement itself (erosions in 6/50, and effusion in 16/50 patients).

Conclusion: Distal lower extremities are indeed frequently involved in RA patients judged by both clinical and ultrasonographic

evaluation. Our study indicates tenosynovitis of foot dorsiflexors is a common US finding in RA patients seen in daily practice.


S213

류마티스 염 환자에서 TNF길항제 투여 후 결핵발생률 연구

건강보험심사평가원 진료심사평가 원회

서 기

배경 목 : 류마티스 염 환자에서 TNF길항제 투여 후 결핵발생률을 TNF 길항제 종류, 잠복결핵 지침 수 여부,

TNF 길항제 투여 후 기간에 따라 알아보고자 하 다.

상 방법: 건강보험심사평가원에 청구된 자료를 분석하여 2007년 1월에서 2010년 12월까지 류마티스 염 상병으로

1회 이상 TNF 길항제를 투여 받은 3,573명을 상으로 하 다. 결핵발생률은 TNF 길항제 종류, 잠복결핵 지침 수 여부,

TNF 길항제 투여 후 기간에 따라 년간 10만 명 당 발생률을 구하 다.

결과: 결핵발생률은 TNF 길항제 투여 후 찰기간 년간 10만명 당 975.2명이었고, 6개월 이내 발생률은 년간 10만

명 당 1,295.1명, 1년 이내 발생률은 1,183.3명이었다. TNF 길항제 종류별 결핵발생률은 년간 10만 명 당 etanercept 739.1명,

infliximab 1,249.5명, adalimumab 1,063.0명이었고, 잠복결핵 지침 수 여부에 따른 결핵발생률은 년간 10만명 당 TNF

길항제 투여 국내 지침에 따라 정기간 정요법으로 잠복결핵 치료를 한 경우 500.1명, TNF 길항제 투여 잠복결핵

검사를 시행하고 잠복결핵 치료는 하지 않은 경우 1,030.1명, 잠복결핵 검사 시행이나 잠복결핵 치료 없이 TNF 길항제를

투여한 경우 1,177.1명이었다.

결론: 류마티스 염 환자에서 TNF 길항제 투여 후 결핵발생률은 사용한 약제, 잠복결핵 지침 수 여부, TNF 길항제

투여 후 기간에 따라 차이가 있었다. etanercept를 투여한 경우, 잠복결핵 치료를 한 경우, TNF 길항제 투여 1년 이후인

경우에 결핵발생률이 낮았고, infliximab를 투여한 경우, 잠복결핵 지침을 지키지 않은 경우, TNF 길항제 투여 6개월 이내

인 경우 결핵발생률이 높았다.


S214

Cancers in RA Patients

Division of Rheumatology, Department of Internal Medicine, Arthritis & Autoimmunity Research Center1, Department of Preventive Medicine, Catholic University of Daegu School of Medicine2, Daegu, Korea

Hwajeong Lee1, Jisuk Bae2, Seong-Kyu Kim1, Jung-Yoon Choe1

Objective: Rheumatoid arthritis(RA) is the most common autoimmune disease and many epidemiologic studies have suggested

the association between rheumatoid arthritis and malignancy. The objective of this study was to investigate overall cancer risk

and risk for specific cancer types in RA patients in Korea.

Method: RA patients, who were diagnosed with the disease between 1996 and 2009 and underwent treatment at our Center,

were selected retrospectively as subjects for the current study. 1,885 patients with RA who were more than 19 years of age

at diagnosis of the disease were enrolled.

Result: During the follow-up period from 1996 to 2009, total 100 incident cancer cases (31 cases for males; 69 cases for

females) have been identified. The total number of follow-up was 10,218.9 person-years (1,341.8 person-years for males; 8,877.1

person-years for females). The overall incident rate of all cancers was 978.6/100,000 (2,310.3/100,000 for males; 777.3/100,000

for females). Seven leading sites of cancer incidence were as follows: for males, lung (10 cases), colon and rectum (5 cases),

stomach (3 cases), prostate (3 cases), Non-Hodgkin’s lymphoma (2 cases), bladder (2 cases), and leukemia (2 cases); for females,

thyroid gland (17 cases), stomach (10 cases), breast (9 cases), cervix uteri (9 cases), Non-Hodgkin’s lymphoma (5 cases),

Gallbladder etc. (4 cases), and colon and rectum (3 cases). Risk for specific cancer types of RA pateints were evaluated comparing

with the general Korean population. Males had greater risks of lung cancer (SIR=5.46, 95% CI: 2.60∼9.36) and leukemia

(SIR=16.7, 95% CI: 1.58∼47.9). Females had increased risk for thyroid cancer (SIR=1.75, 95% CI: 1.02∼2.68), cervical cancer

(SIR=3.65, 95% CI: 1.65∼6.42), Non-Hodgkin’s lymphoma (SIR= 6.47, 95% CI: 2.04-13.4).

Conclusion: We investigated cancer types and numbers occurred in RA patients in Korea and also evaluated the risk for specific

cancer types of RA patients.


S215

Vitamin D Deficiency Can be a Risk Factor for the Presence of Rheumatoid Arthritis Among Patients with Inflammatory Arthritis

Division of Rheumatology, Department of Internal Medicine, Pusan National University School of Medicine1, Division of Rheumatology, Department of Internal Medicine, Kosin University College of Medicine2,

Young-Do Hospital3, Busan St. Mary’s Medical Center4, Ilsin Christian Hospital5, Busan, Malgeunsam Hospital6

, Changwon, Korea

Seung-Geun Lee1, Geun-Tae Kim2, Seong-Hu Park3, Joung-Wook Lee4, Jun-Hee Lee

5, Seung-Hoon Baek

5, Young-Eun Park

6

Objectives: Although vitamin D deficiency is reported to be common in patients with various rheumatic diseases, little is known

about the relationship between vitamin D deficiency and the risk of rheumatoid arthritis (RA). The aim of our study is to inves-

tigate whether vitamin D deficiency is a risk factor for RA among patients with inflammatory arthritis.

Materials and Methods: With a retrospective setting, one hundred-one patients with inflammatory arthritis who had at least

1 swollen joint and no history of previous rheumatic and musculoskeletal diseases included our study. All participants were consec-

utively recruited at a university-affiliated rheumatology center in South Korea from March 2012 to February 2013. Participants

taking vitamin D supplements or having arthritis more than 6 months were excluded. At first visit, serum 25(OH) vitamin D

levels of entire study population were measured. RA was classified according to the 2010 American College of Rheumatology/

European League Against Rheumatism (ACR/EULAR) criteria.

Results: Mean age of participants was 56.5 (±12.2) years and 85.1% was female. Thirty eight (37.1%) subjects were categorized

as RA. Serum 25(OH) vitamin D levels were inversely correlated with the titer of anti-citrullinated protein antibody (ρ=－0.214,

p=0.031), swollen joint count (ρ=－0.196, p=0.049) and patient’s visual analogue scale (ρ=－0.202, p=0.043). Low serum

25(OH) vitamin D levels tended to be related to a greater likelihood of the fulfillment the 2010 ACR/EULAR criteria among

patients with inflammatory arthritis after adjusting confounders (OR=0.952, 95% CI=0.905∼1.001, p=0.054). Especially, severe

vitamin D deficiency (25(OH) vitamin D＜10 ng/mL) was significantly associated with diagnosing RA in multivariable logistic

regression analysis (OR=3.259, 95% CI=1.137-9.342, p=0.028).

Conclusions: Our findings suggest that low serum vitamin D levels would contribute the presence of RA among inflammatory

arthritis patients.


S216

The Association of Serum Vitamin D and 10-year Cardiovascular Risk in Patients with Rheumatoid Arthritis


정승민ㆍ이재호ㆍ서 선ㆍ고정희ㆍ이주하ㆍ곽승기ㆍ박경수ㆍ박성환

Background: Vitamin D deficiency is associated with increased cardiovascular (CV) risk. Rheumatoid arthritis (RA) is an in-

dependent risk factor for CV diseases, and there are some reports of lower level of vitamin D in patients with RA.

Objectives: This study was aimed to evaluate the correlation of serum vitamin D and 10-year CV risk in patients with RA.

Methods: 236 patients with RA were included for the analysis. For the study population, clinical parameters and CV risk factors

were recorded, and serum level of 25(OH)vitamin D was measured. 10-year CV risk was calculated by the Systematic Coronary

Risk Evaluation (SCORE) model.

Results: Of 236 patients, 202 patients (85.6%) were women, and the mean age was 56.3 years. The median duration of disease

was 6.1 years. Eleven patients (4.7%) were current smokers, and 10 patients (4.2%) had a history of established coronary heart

disease or stroke. The prevalence of hypertension, diabetes, and dyslipidemia were 33.5% (n=79), 7.6% (n=18), and 28.0% (n=66),

respectively. The median of 10-year CV risk from SCORE system was 1% (range 0∼11). The level of serum 25(OH)vitamin

D was lower than 10 ng/mL in 15.5% of patients, and higher than 30 ng/mL in 6.6% of patients. The median level of serum

25(OH)vitamin D was 14.6 (interquartile range 10.9∼20.1). Serum level of vitamin D was negatively correlated to 10-year CV

risk estimated by SCORE (r=0.803).

Conclusions: Our results show the strong correlation of serum vitamin D level and estimated 10-year CV risk. More inves-

tigations are required to elucidate the underlying mechanism and to evaluate the effect of vitamin D supplementation on CV

risk.


S217

Association of Body Mass Index with Disease Activity in Patients with Rheumatoid Arthritis: Focus on Disease Activity Indices and Composites

Division of Rheumatology, Department of Internal Medicine, Arthritis & Autoimmunity Research Center, Catholic University of Daegu School of Medicine, Daegu, Korea

Jung-Yoon Choe, Hwajeong Lee, Seong-Kyu Kim

Objective: The debate regarding the influence of body mass index (BMI) on clinical disease activity in rheumatoid arthritis

(RA) remains unsolved. This study investigates whether BMI is associated with disease activity composites and clinical parameters

in Korean patients with RA.

Methods: A total of 568 patients with RA were consecutively enrolled in this study. BMI and disease activity composites

including the Disease Activity Score (DAS28) and the Clinical/Simplified Disease Activity Index (CDAI/SDAI) were assessed.

Statistical analyses were performed using Chi-square, one-way ANOVA, and multivariate regression analyses.

Results: The mean BMI was 22.3 kg/m2 (SD 3.1). Swollen joint count was significantly different among the four BMI categories

(p=0.038). About 60.6% (n=344) of enrolled patients fell into the underweight and normal BMI categories. Multivariate regression

analysis showed a negative correlation of BMI and erythrocyte sediment rate (ESR) in all patients (B=－0.011, p=0.049). In

male patients, lower BMI was associated with longer disease duration (B=-0.226, p=0.002). The higher trend for negative associa-

tion between BMI and ESR in the non-remission group (n=410) indicates that lower BMI patients have an increased tendency

for higher disease activity, especially uncontrolled disease activity.

Conclusion: This study provides some evidence for in part close association between BMI and disease activity of RA, although

only ESR was found to be associated with BMI, especially in uncontrolled activity patients.


S218

Association Between Vitamin D Deficiency and Obesity in Patients with Rheumatoid Arthritis

Division of Rheumatology, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Korea

Jae Ho Lee, Jung Hee Koh, Young Sun Suh, Jennifer Lee, Seung-Min Jung, Seung-Ki Kwok, Kyung-Su Park, Sung-Hwan Park

Background: Vitamin D deficiency is broadly associated with four clinical features in RA patients, high disease activity, physical

disability, high cardiovascular disease risk, and osteoporosis [1-3]. To lower above morbidities, vitamin D deficiency can be

overcome through vitamin D supplement although RA itself cannot be modifiable.

Objective: To determine risk factors related low serum 25-hydroxyvitamin D (25(OH)D) concentration and intervening factors

to lowering the response of vitamin D supplement in low disease activity rheumatoid arthritis (RA) patients.

Method: In 448 established RA with remission or low disease activity, serum 25(OH)D concentration measurement were per-

formed using commercial chemiluminescence immunoassay (CLIA). Bone mineral density (BMD) was measured using dual-energy

X-ray absorptiometry. Age, sex, menopause, hormone replacement, body mass index (BMI), disease duration, fracture risk assess-

ment tool (FRAX), tumor necrosis factor-α (TNF-α) antagonist therapy and others were investigated as variables.

Results: Prevalence of vitamin D (25(OH)D) deficiency (＜20 ng/mL) were 339 (75.6%). BMI in vitamin D deficiency group

was higher than normal vitamin D group (p=0.006). In patients without vitamin D supplement, gender (p=0.002) was an important

factor to decide whether vitamin D deficiency or not by multivariate logistic regression. However, obesity (p=0.022) was sig-

nificant factor related vitamin D deficiency in vitamin D supplement group. Obesity (BMI ≥25) showed 2.523 (p=0.021) odd

ratio about vitamin D deficiency compared with not obese BMI patients in vitamin D supplement group. Despite receiving vitamin

D supplement, BMI increase had higher risk vitamin D decrease, odd ratio 3.818 (p=0.028).

Conclusion: Vitamin D supplement is important treatment to correct serum 25(OH)D concentration in RA. Even if a patients

is treated with vitamin D supplement, it can hardly hope to ameliorate serum 25(OH)D concentration in obese condition.


S219

Prognostic Impact of Functional Outcome in Patients with Rheumatoid Arthritis - Prospective Cohort Study

Division of Rheumatology, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea

Na Ri Kim, Jung Soo Eun, Sang Hoon Kwon, Churl Hyun Im, Eon Jeong Nam, Young Mo Kang

Background and Purpose: Patients with rheumatoid arthritis (RA) share an increased risk of mortality, which has been partially

attributed to higher cardiovascular mortality. To determine the mortality and cause of death over 2 years in a cohort followed

prospectively.

Methods: Mortality in 406 RA patients and 218 age and sex matched normal controls enrolled from 2009 to 2011 in the KNUH

Atherosclerosis Risk in RA (KARRA) cohort was assessed according to a standardized protocol for 2 years.

Results: A total 10 deaths occurred among RA patients during 2 years follow-up period while there was no deaths among

the controls. Disease duration of RA until death was 32.3±34.0 years and causes of death included infection (6 pneumonia and

2 septic shock), sudden cardiac death (1 patient), and others (2 patients). Mortality was associated with higher fasting blood

sugar among conventional cardiovascular risk factors. RA-associated variables including functional class, modified Korean version

of HAQ, ESR, CRP, and ESR-area under the curve (AUC) were significantly associated with mortality after the adjustment

with age and gender. After multivariate analysis, only mKHAQ was found to be significantly associated with mortality (P=0.012).

Among the patients with HAQ ＜19, no death occurred in patients with normal ESR, while 3 deaths in patients with abnormal

ESR. Mortality was highest among patients with HAQ ≥19 and abnormal ESR (6 deaths among 41 patients, 14.6%).

Conclusions: These results suggest that functional outcome of RA has a critical prognostic impact, and tight control of in-

flammation may improve survival in this populations.


S220

Impact of Etanercept-Methotrexate Therapy on Patient-Reported Outcomes in Moderately Active Rheumatoid Arthritis:

Korean Results from the Induction Period of Preserve Trial

Department of Rheumatology, Yeonsei University College of Medicine1, Department of Rheumatology, Konkuk University School of Medicine2, Department of Rheumatology, Hallym University Sacred Heart Hospital3,

Department of Rheumatology, Kangdong Sacred Heart Hospital4, Pfizer Pharmaceuticals Korea Limited

5, Korea

Min-Chan Park1, Sang-Heon Lee2, Hyun Ah Kim3, In-Je Kim4, Hyun-Jeong Yoo5

Background: Patients with RA experience impairment in physical function and health-related quality of life, which may reduce

productivity at work. Biologic agents have primarily been assessed in patients with severe RA, while limited data exists on their

effect on clinical and functional status in moderate RA.

Objectives: This analysis evaluates the effects of etanercept (ETN) plus methotrexate (MTX) for 36 weeks on patient-reported

outcomes (PROs) in Korean patients with moderate disease activity despite MTX.

Methods: Subjects with DAS28 ＞3.2 and ≤5.1 despite oral MTX received open-label ETN 50 mg QW plus MTX (titrated

to ≤25 mg/wk as needed through wk 28) for 36 weeks. PROs included total HAQ, EQ-5D, FACIT-Fatigue, Brief Pain Inventory

(BPI), subject global assessment of disease activity and WPAI. Analysis of Korean subjects in the modified intent to treat pop-

ulation (last observation carried forward) was conducted.

Results: At baseline (n=98), most subjects were female (79%), RF+ (75%), and ACPA+ (82%); 40.6% were employed. Mean

age was 47yrs; DAS28, 4.3 and HAQ, 1.2. In addition to significant improvements in disease activity, at week 36, 49% of

subjects achieved total HAQ＜0.5 (p＜0.0001); with significant improvements seen in EQ5D (p=0.0008) and FACIT-Fatigue (p

＜0.0001) scores. Significant improvements in percent change from baseline were also observed at week 36 in BPI (p＜0.0001)

and subject global assessment (p＜0.0001). Significant declines in the overall work impairment component of WPAI (p=0.0001)

and in mean% work time missed due to RA were observed (baseline=13.8%; week 36=6.6%; p=0.008).

Conclusions: Combination ETN-MTX treatment for 36 weeks in Korean subjects with moderately active RA despite MTX

provided significant improvements in physical function, pain, fatigue, HR-QoL, and work productivity. These outcomes indicate

therapeutic benefits beyond clinical and radiographic improvements reported previously and support a role for this therapeutic

approach in patients with less severe disease.


S221

Immunogenicity of Anti-tumor Necrosis Factor Therapy in Korean Patients

가톨릭 학교 의과 학 내과학교실 류마티스내과1, 순천향 학교 의과 학 내과학교실 류마티스내과2, 건국 학교 의과 학 내과학교실 류마티스내과3

정승민1ㆍ김 숙2ㆍ김해림3ㆍ곽승기1ㆍ박경수1ㆍ박성환1ㆍ김호연3ㆍ주지 1

Introduction: Immunogenicity of anti-tumor necrosis factor (anti-TNF) therapy is considered to be an important mechanism

underlying treatment failure. However, there is limited data concerning the difference in generation of anti-drug antibody (ADA)

according to drugs and diseases.

Objective: The aim of this study is to compare the prevalence of ADA formation between patients with rheumatoid arthritis

(RA) and ankylosing spondylitis (AS), and among groups treated with different TNF inhibitors.

Methods: 183 patients with RA and 177 patients with AS was enrolled for the evaluation of immunogenicity. Clinical profiles

of study population were examined at initiation of TNF inhibitors. The positivity of ADA against TNF inhibitors was determined

using ELISA method.

Results: Of 360 patients, ADAs were detected in 35 patients: 17 with RA and 18 with AS. The prevalence of ADA was

highest in patients who treated with infliximab (35.0% and 25.6% in patients with RA and AS, respectively), followed by adalimu-

mab (9.8% in RA and 9.9% in AS) and etanercept (2.5% in RA and 0% in AS). In patients with RA, the positivity of ADA

was related to the class of TNF inhibitors (p＜0.0001), treatment failure (p=0.016), and discontinuation of anti-TNF therapy

(p=0.030). Also in patients with AS, the association of ADA with type of drugs (p＜0.0001) and withdrawal of treatment (p=0.049)

was identified. The prevalence of ADA was not significantly different between patients with RA and AS when adjusting the

other variables (p=0.690). Comparison between drugs showed intermediate prevalence of ADA in patients treated with adalimumab

(referent), highest prevalence (odds ratio [OR] 8.378, 95% confidence interval [CI] 1.828∼38.395), and significantly lower preva-

lence in patients with etanercept (OR 0.245, 95% CI 0.109∼0.548).

Conclusions: Our result shows the different immunogenicity of TNF inhibitors and insignificant effect of disease type on

immunogenicity. More investigations are required to determine the clinical profiles for prediction of ADA formation.


S222

Growth Arrest-Specific 6 (GAS6) Gene Polymorphisms are Associated with Clinical Manifestations of Systemic Lupus Erythematosus in Koreans

Department of Rheumatology, Ajou University School of Medicine, Suwon, Korea

Ja Young Jeon, Bong-Sik Kim, Chang Hee Suh

Backgrounds: Growth Arrest–Specific 6 (GAS6) can regulate the inflammatory response by downregulating TNF-α, IL-6 and

interferon secretion in dendritic cells, and, interestingly, animals lacking the TAM (Tyro-3, Axl and Mer) family of receptors

develop autoimmune diseases. A recent study reported that Gas6 is important in clearance of debris and regulation of the innate

immune system in patients with SLE.

Objectives: We have identified single nucleotide polymorphisms in the GAS6 gene, determined their frequency in Korean pop-

ulation, and elucidated their pathogenic role and clinical significance in Korean SLE patients.

Methods: Two hundred ninety-seven SLE patients and 215 normal controls were enrolled from the rheumatology clinic at the

Ajou University Hospital. Gas6 genes located between exon15 and 3' flanking region were amplified by polymerase chain reaction.

We identified possible polymorphisms in the GAS6 gene and that were screened by direct sequencing. Additionally, SNP genotyp-

ing was performed by using the SNaPSHOT assay.

Results: We have screened the GAS6 gene located between exon 15 region and 3’UTR region. We have identified eleven

polymorphisms (rs76238089, rs11541918, rs1131227, rs7489780, rs3209879, rs34766013, rs11843390, rs11843762, rs77218634,

rs72670681 and rs76231477) in the Gas6 gene. However, only rs11843762 T/C polymorphism of the 3' flanking region in the

Gas6 gene was identified as SNP in Koreans. There were no significant differences between SLE and NC in the observed genotype

frequencies. In the rs11843762 T/C polymorphism, lymphopenia was significantly more common in the SLE patients with the

rs11843762 C allele (p=0.039).

Conclusions: These results indicate that the Gas6 gene polymorphisms are very rare in Korean population. And these data

suggest that genetic polymorphisms of GAS6 gene may be associated with disease phenotypes of SLE in Koreans.


S223

Autoantibodies to C-reactive Protein may not Predict the Progression of Incomplete Lupus to Systemic Lupus Erythematosus

Department of Rheumatology, Ajou University School of Medicine, Korea

Ju-Yang Jung, Bo-Ram Koh, Chang-Bum Bae, Hyoun-Ah Kim, Ja-Young Jeon, Chang-Hee Suh

Anti-CRP antibodies have been described in patients with systemic lupus erythematosus (SLE) and their presence has been asso-

ciated with disease activity. We investigated the anti-CRP antibody as a disease activity marker in Korean patients with SLE.

Blood samples were collected from patients with SLE (n=99) and those with lupus syndrome (n=60) satisfying only 2~3 ACR

criteria for the classification of SLE, and normal healthy controls (NC, n=48). The anti-CRP antibody levels in the SLE group

(35.6±35.1 AU) were higher than those in the lupus syndrome (23.1±25.8 AU, p=0.016), and NC groups (21.0±14.3 AU, p＜0.001).

However, only 18 patients with SLE (19%) revealed positive anti-CRP antibodies. Anti-CRP antibody levels were significantly

higher in patients with SLE and arthritis than in those without arthritis. A marginally significant correlation was found between

the level of anti-CRP antibodies and leukocytes, platelets, C-reactive protein, complement 3, complement 4, anti-dsDNA antibody,

antichromatin antibody, and SLEDAI. No significance difference in anti-CRP levels was observed in patients with lupus syndrome

whether they progressed to SLE or not. These data suggest that anti-CRP antibodies appear not to be a useful biomarker to aid

in the assessment of SLE, nor can they predict which patients with lupus syndrome will progress to SLE.


S224

Anti-ribosomal P Antibody may be Associated with Protective Role in Patients with Lupus Nephritis



1, Yong-Wook Park

1, Ji Shin Lee

2, Yoo Duk Choi

2, Shin-Seok Lee

1

Purpose: Anti-ribosomal P antibody (Anti-P) was suggested as a possible biomarker in LN. In diverse studies, anti-P was related

with renal flare, activity, and also histopathologic findings. Recent study showed anti-P in the absence of anti-dsDNA was a

valuable marker to predict a better long-term outcome in LN. The aim of this study was to define clinical, histopathologic, and

prognostic differences according to the presence of anti-P in Korean patients with biopsy-proven LN.

Methods: We studied 79 patients who had kidney biopsy prior to the start of induction treatment, and who subsequently were

treated with immunosuppressive drugs for at least 6 months. Sociodemographic, clinical, and treatment-related data were obtained

by reviewing patients’ charts. All biopsy specimens were reviewed in a blinded manner by 2 pathologists, according to the 2004

ISN/RPS criteria. Anti-P was detected by immunoblot analysis. Kaplan-meier analysis was used to compare the probability of

progression to chronic renal disease according to presence of anti-P.

Results: Twenty eight patients (35.4%) of 79 patients had anti-P. In demographic and clinical features, the patients with anti-P

showed earlier onset of LN (26.6±10.1 versus 34.7±12.1, P=0.005), and higher SLEDAI score, and also higher eGFR level at

the time of renal biopsy than those without that antibody. The antibody profiles of the patients were similar except anti-Sm

antibody. In the histopathologic findings, the patients with anti-P showed less interstitial inflammation in activity index, less glo-

merular sclerosis, less tubular atrophy, and less interstitial fibrosis in chronicity index. Furthermore, anti-P was associated with

lower chronicity scores, After a median follow-up period of 47 months, renal function was preserved in 27 of 28 (96.4%) patients

who had anti-P, but 13 of 51 (74.5%) patients without anti-P did not progress to chronic renal disease.

Conclusion: Our findings suggest that anti-P was related with better histologic findings and associated with favorable renal

outcome in Korean patients with LN.


S225

신홍반루푸스 환자에서 경동맥 경직도와 경동맥 동맥경화와의 련성

메리놀병원 류마티스내과

이홍직ㆍ이지

Objective: Although a series of trials support the intima-media thickness (IMT) of carotid artery as a good predictor for the

cardiovascular events in patients with systemic lupus erythematosus (SLE), the link between IMT, vascular elastic property and

the disease activity of SLE is not well defined. We investigated the association between carotid atherosclerosis, elastic properties

of the carotid arterial wall and clinical parameters of SLE.

Methods: Fifty-one SLE patients and fifty healthy controls were included. Peak systolic global circumferential and posterior

radial strains of carotid artery were measured to assess the elastic properties. Beta stiffness index was used as conventional method

for the distensibility of the carotid artery. Information concerning SLE duration, cumulative dose of steroids and/or im-

munosuppressive drug intake was recorded, and SLE activity was assessed by SLE disease activity index (SLEDAI) score.

Results: Carotid plaques were more common in SLE patients. SLE patients with plaques were older and showed the increased

mean IMT, high sensitivity C-reactive protein (hs CRP), IgG anti-cardiolipin antibody (aCL), and longer disease duration compared

with those without plaques. Peak systolic global circumferential and posterior radial strain as well β stiffness index were sig-

nificantly lower in SLE group. Age, disease duration, hsCRP, IgG aCL showed significant correlations with mean IMT and param-

eters of carotid elastic property (all P’s＜0.05).

Conclusions: Carotid atherosclerosis was more common in SLE patients, and carotid arterial stiffness had significant correlation

with disease duration, hsCRP and IgG aCL level. Speckle tracking strain imaging is a comparative method for the assessment

of elastic properties of carotid artery of SLE patients.


S226

Association Between Arterial Stiffness and Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus


이홍직ㆍ이지

Background: Although pulmonary arterial hypertension (PAH) is a severe manifestation of systemic lupus erythematosus (SLE),

the pathogenesis of PAH associated with SLE is yet unclear. The aim of the study is to evaluate the role of arterial stiffness

in PAH in SLE patients using strain echocardiography, and correlating it with inflammatory parameters of the disease.

Methods: Measurement of arterial stiffness carotid artery strain parameters and Doppler echocardiography was performed in

fifty patients with SLE. PAH was diagnosed if the pulmonary artery systolic pressure (PAPS) was more than 40 mmHg.

Information concerning SLE duration, medication, and autoantibodies were checked. SLE activity was assessed by SLE disease

activity index (SLEDAI).

Results: In fifty SLE patients, PAH was detected in 6 patients (12%). Although there were no differences in blood pressure,

inflammatory marker, disease duration, prevalence of Raynaud phenomenon, and SLEDAI between SLE patients with PAH and

without PAH, anticardiolipin antibody (IgG aCL) and parameters of carotid artery deformation were reduced in patients with

PAH (all P’s＜0.05). Univariate and multiple regression analysis revealed that the only significant independent predictors of pres-

ence of PAH were carotid circumferential/radial strain and IgG aCL.

Conclusion: Our study suggests that PAH in SLE may not be related to underlying autoimmune process and increased arterial

stiffness from SLE might contributes to the pathogenesis of PAH related to SLE. Also, the significant association of anticardiolipin

antibodies with SLE-related PAH cases suggests that thrombosis may play an important role in PAH with SLE.


S227

Smoking Increases Systemic Lupus Erythematosus Susceptibility

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Korea

Ji-Young Choi, So-Young Bang, Hye-Soon Lee, Sang-Cheol Bae

Background: Smoking has been suggested as a risk factor for SLE. Several studies investigated the association between smoking

and SLE, but results were less clear.

Objectives: We investigated whether HLA-DRB1 risk alleles, smoking, or the combination contribute to the development of

SLE and whether smoking influences the production of autoantibodies in a Korean population.

Methods: A total of 877 women from BAE SLE cohort, who fulfilled the ACR 1997 revised criteria for SLE, and 976 healthy

women were recruited in a Korean population. Four-digit HLA-DRB1 typing was performed by a conventional PCR-SBT method.

Smoking history was obtained through a questionnaire by face-to-face interviews.

Results: HLA-DRB1*15:01 (OR 1.82; 95% CI 1.44, 2.03) and HLA-DRB1*08:03 (OR 1.81; 95% CI 1.40, 2.34) alleles were

associated with SLE susceptibility, using the relative predispositional effects according to controlling the Bonferroni method.

Smoking had significant effects on the development of SLE [OR 2.50 (95% CI: 1.48∼4.21), p=6.23×10-4] adjusted for age and

HLA-DRB1 risk alleles. The combination of smoking and HLA risk allele increased the risk for SLE 5.7-fold, compared with

nonsmokers without carrying HLA-DRB1 risk alleles. We found no significant relationship between smoking and the production

autoantibodies, such as anti-Sm, ds-DNA, anti-Ro, anti-La, anti-RNP, or anti-phospholipid antibody.

Conclusion: Smoking had significant effects on the development of SLE and the DRB1*1501 and *0803 alleles were associated.

The combination of smoking and HLA risk allele increased the risk.


S228

Pregnancy Outcomes in Korean Patients with Systemic Lupus Erythematosus and Antiphospholipid Antibodies: A Single Center Experience

Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University1, Department of Obstetrics and Gynecology, College of Medicine, Catholic University2

, Seoul, Korea

Jung Hee Koh1, Hyun Sun Ko2, Jae Ho Lee1, Jennifer Lee1, Seung Min Jung1, Young Sun Suh1, Seung-Ki Kwok1, Kyung-Su Park1, Sung-Hwan Park1

Background and Objectives: Recently, there was a prospective observational study related with the presence of lupus anti-

coagulant (LAC) predict of adverse pregnancy outcome in patients with antiphospholipid antibodies. As comprehensive data are

lacking in Koreans, the aim of this study was to investigate which serologic and clinical findings affect on disease flares and

adverse pregnancy outcomes in systemic lupus erythematosus(SLE) pregnancies with antiphospholipid antibodies in Korea.

Methods: We performed a retrospective analysis of 206 SLE pregnancies during 15-year period (1998-2012) to describe the

clinical features, maternal and fetal outcome in Catholic University Medical center. Lupus activity was based on SLE Disease

Activity Index (SLEDAI) criteria. The relationship between variables and adverse pregnancy outcome was assessed by bivariate

and multivariate analysis.

Result: Of patients with LAC in SLE pregnancies, 79.9% (107/134) gave fewer live births (p=0.039) and 36.6% (49/134) showed

more active disease at conception (p＜0.0001) to compare with the patients without LAC. 59.7% (80/134) had disease flare during

pregnancy (p＜0.0001). However, LAC did not predict adverse pregnancy outcome, disease flare, and maternal outcome.

Conclusion: LAC was related fewer live births, more active disease at conception, and disease flare during pregnancy in SLE

patients.


S229

Increased Expression of Interleukin 33 in Sera and Salivary Gland from Patients with Sjogren Syndrome


정승민ㆍ이재호ㆍ서 선ㆍ고정희ㆍ이주하ㆍ박경수ㆍ박성환ㆍ곽승기

Background: Interleukin 33 (IL-33), a member of IL-1 superfamily, exerts pro-inflammatory effect by binding with ST2 ex-

pressed on many cell types. Recently, the association of IL-33 with autoimmune disease has been increasingly reported.

Objective: The aim of this study is to identify the expression of IL-33 and ST2 in sera and salivary gland tissues from patients

with Sjogren syndrome (SS).

Methods: Serum IL-33 and was measured in patients with and without SS. Expression of IL-33 and ST2 in salivary gland

tissue from patients with and without SS was assessed by immunohistochemistry. The source of IL-33 in salivary gland of patients

with SS was investigated using confocal microscopy system after staining with cytokeratin antibody, CD31 antibody and IL-33

antibody. Additionally, we examined the expression of IL-33 mRNA and ST2 mRNA. The level of IL-33 mRNA in salivary

gland cell line (human head and neck squamous cell carcinoma A253 cell) was determined after stimulation with inflammatory

cytokines. Also, we measured the level of ST2 mRNA from peripheral blood mononuclear cell (PBMC) isolated from blood

of patients with and without SS.

Results: Serum IL-33 level was significantly higher in SS group than that of control group (p=0.004). Immunohistochemistry

of salivary gland revealed increased expression of IL-33 and ST2 in SS group. We demonstrated the expression of IL-33 in

epithelial and endothelial cells from salivary gland of patients with SS. The expression of IL-33 mRNA in A253 cell was consid-

erably increased after stimulation with interferon gamma. The level of ST2 mRNA in PBMC was higher in SS group than control

group, although statistically not significant (p=0.093).

Conclusions: Our result indicates that IL-33 is involved in the pathogenesis of SS. Further research would suggest a new ther-

apeutic approach associated with IL-33/ST2 pathway in SS.


S230

Impact of Fractalkine (CX3CL1) in Primary Sjogren’s Syndrome: Its Expression in Labial Salivary Gland

Division of Rheumatology, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Korea

Jae Ho Lee, Jung Hee Koh, Young Sun Suh, Jennifer Lee, Seung-Min Jung, Kyung-Su Park, Sung-Hwan Park, Seung-Ki Kwok

Background: Sjögren’s syndrome in humans is an organ-specific autoimmune disorder characterized by lymphocytic infiltration

and destruction of the lacrimal and salivary glands. Chemokines are small chemoattractant cytokines that induce leukocyte accumu-

lation at inflammatory sites and modulate inflammatory activities through the recruited cells. Fractalkine is a member of the

CX3C family. Fractalkine is considered especially important for the recruitment of Th1 type cells and is a strong candidate for

directing pathologic mononuclear cell infiltration.

Objectives: To identify the expression of fractalkine in human salivary gland and serum in SS. To investigate the cell type

expressing CX3CR1 in peripheral blood mononuclear cell with SS.

Methods: Serum fractalkine level was determined by ELISA. Immunohistochemical stain was done to compare the expression

of fractalkine and CX3CR1 between salivary gland of SS and control. The cells to be merged with fractalkine were evaluated

by confocal microscopy. Cytokine-stimulated fractalkine expression was quantified by QPCR and ELISA, using A253 cell line.

We investigated CX3CR1expressing cell in human PBMC by QPCR and flow cytometry.

Results: There was a significantly increased serum fractalkine level in SS compared with control. It showed increased expression

in fractalkine and CX3CR1 in SS salivary gland rather than control by immunohisto-chemical stain. Fractalkine and CX3CR1

positive cell count showed a tendency to increase as higher grade in SS salivary gland. In confocal microscopy, epithelial cell

and fractalkine was merged together, but not endothelial cell in SS salivary gland. Only IFN-γ stimulation induced upregualtion

of fractalkine expression in A253 cell line, but not IL-1ß and TNF-α. However, CX3CR1 expression in PBMC did not show

significant difference between SS and control.

Conclusions: Salivary gland of SS expresses high level of fractalkine and CX3CR1. Histologic grade is proportional to ex-

pression of fractalkine and CX3CR1. Main cell of fractalkine production are epithelial cell in SS salivary gland.


S231

Microvascular Findings in Patients with Raynaud’s Disease - Assessed by Nailfold Capillaroscopy and Flow Mediated Dilatation


이홍직ㆍ이지

Objectives: Nailfold capillaroscopy (NC) represents the method to analyze microvascular abnormalities in autoimmune rheumatic

diseases, but the pathophysiological link between the microvascular derangement which is seen in NC and endothelial function

is yet to be discovered. We investigated the association between endothelial function which is assessed by brachial artery

flow-mediated dilatation (FMD) and NC patterns in patients with Raynaud’s phenomenon (RP).

Methods: 37 postmenopausal women with secondary RP and 23 controls suffering from hand numbness were evaluated with

NC using a digital microscope at 400× and 100 × magnifications. The microvascular alterations were classified into three different

patterns, early, active and late. Endothelial function was examined by brachial FMD (endothelium dependent) and response to

40 μg of sublingual nitroglycerine (NTG-induced dilatation, endothelium independent).

Results: There were significant capillary loop dilatation (apical width; 14.1±5.6 vs. 10.4±1.7 μm, p=0.001 and total width;

40.6±15.1 vs. 31.6±4.6 μm, p=0.002) and length (316.0±78.5 vs. 270.4±34.7 μm, p=0.004) in secondary RP compared to controls.

Giant capillaries, loss of capillaries, hemorrhage and background pallor were much more prevalent in secondary RP as compared

to controls (all P’s＜ 0.05). Although there were no significant differences in NTG-induced dilatation between secondary RP and

controls (16.1±5.9% vs. 19.6±9.0%, P=0.091), significant decreases in the FMD value (6.1±3.5% vs. 9.0±2.2%, p＜0.001) were

noted. Both FMD and NTG-induced dilatation showed a significant inverse association with severity of NC findings (r=-0.355,

p=0.005 and r=-0.285, p=028).

Conclusions: Significantly impaired endothelial function was found in secondary RP and capillary enlargement was significantly

associated with endothelial dysfunction.. This result might implicate that the recognition of abnormal capillaroscopic patterns in

the secondary RP might be prognostic for the early detection of microvascular heart involvement.


S232

Cross-cultural Adaptation and Validation of a Korean Version of the Behcet’s Disease Current Activity form 2006

Gachon University Gil Medical Center, Korea

Hyo Jin Choi, Suk Ho Kang, Mi Ryung Seo, Hee Jung Ryu, Han Joo Baek

Objective: This study was to perform a cross-cultural adaptation of the Behcet’s disease current activity form (BDCAF, version

2006) to Korean language and to evaluate its reliability and validity in a population of Korean patients with Behcet’s disease

(BD).

Methods: The BDCAF was translated into the Korean language by two translators, who were aware of its objectives and it

was translated back into the English language by two different translators. The Korean BDCAF was administered to fifty-four

patients with BD who were attending the outpatient rheumatology clinic. The second BDCAF was done by mail in forty-seven

patients (87%) one day after visit. The test-retest reliability was analyzed by computing k statistics. Kappa scores higher than

0.6 indicated good agreement. To assess validity, we compared BDCAF score with the patient’s/clinician’s perception of disease

activity (0∼7 visual scale) and Korean version of behcet’s disease quality of life (BDQOL) which was validated at 2008.

Results: The male to female was 16:38, and the mean age of patients was 49.0±9.9 years (±SD). The mean disease duration

was 5.4±4.9 years. About test-retest reliability, good agreement were achieved BDCAF items of headache, mouth/genital ulcer,

skin pustules, arthritis and diarrhea with altered/frank blood per rectum, moderate agreement were erythema nodosum, arthralgia

and eye involvement, fair agreement was nausea/vomiting/abdominal pain (all p＜0.005), and poor agreement were nervous system

and major vessel involvement items. Significant correlations were obtained BDCAF score with the patient’s/clinician’s perception

of disease activity and BDQOL (all p＜0.05).

Conclusion: The Korean version of BDCAF is a reliable and valid instrument for measuring current activity in BD patients

of Korea.


S233

Pilot Trial of Tocilizumab for Refractory Patients with Adult Onset Still’s Disease

Division of Rheumatology, Department of Internal Medicine, The Hospital for Rheumatic Disease, Hanyang University School of Medicine, Korea

Jin-Ju Kim, Tae-Hwan Kim, Dae-Hyn Yoo

Background & Objective: Adult onset Still’s disease (AOSD) is a systemic inflammatory disorder with unknown etiology.

As therapeutic agents, traditional disease modifying anti-rheumatic drugs (DMARDs) or biological agents are suggested for patients

unresponsive to corticosteroid. IL-6 plays a pivotal role in the pathogenesis of AOSD among important cytokines. Several case

reports have suggested that tocilizumab, a humanized anti-IL-6 receptor antibody was effective for intractable AOSD. Here, we

described the clinical course of refractory Korean patients treated with tocilizumab therapy.

Methods: The 8 patients who were refractory to DMARDs and/or etarnecept or dependent to corticosteroid were enrolled for

tocilizumab therapy after informed contents. Tocilizumab at 8 mg/kg was administered every 4 weeks.

Results: Six females and 2 males were treated with tocilizumab. The mean age was 33.8 (26∼47) years old. The frequency

of tocilizumab therapy was an average of 6.3 times. Almost patients showed complete (50.0%) or partial (37.5%) response to

tocilizumab therapy except one patient (Table 1). The clinical symptoms improved in 4 weeks (mean), erythrocyte sedimentation

rate (ESR) and C-reactive protein (CRP) improved in 6.3 weeks, respectively. Serum ferritin, IL-18 and IL-6 levels slowly im-

proved within 9.3 weeks, 12.5 weeks and 9.3 weeks, respectively. Three patients discontinued tocilizumab therapy although they

showed improvement of clinical symptoms; because of severe headache and chest discomfort at 12 weeks, neutropenia at 8 weeks,

and severe hepatotoxicity at 8 weeks, respectively. Other adverse events such as mild dizziness, hair loss, weight gain and transient

leucopenia were observed and those were tolerable during follow-up.

Conclusions: Tocilizumab could be a new therapeutic option for AOSD patients refractory to conventional therapy. However,

further clinical trials for efficacy and safety of tocilizumab in patients with AOSD are needed.


S234

강직성 척추염의 활액막 세포에서의 TLR2와 TLR 4의 발


이상엽ㆍ배재호ㆍ임상우ㆍ이성원ㆍ정원태

배경: 강직성 척추염의 발생 기 은 아직 밝 져 있지 않지만 최근에는 HLA-B27 유 자와의 련성에 외부의 자극에

의해 발병하는 것으로 추측되고 있으며 이 외부의 자극 에서 감염이 요한 원인으로 작용하는 것으로 추정되고 있다.

이에 자들은 cell mediated immunity 의 기 에서 처음으로 외부의 자극(감염)을 인지하는 수용체(pattern recognition

receptor) TLR의 발 을 강직성 척추염의 활액막 세포에서 찰하고자 한다.

목 : 강직성 척추염 활액막 세포에서 TLR의 발 을 규명하고, TLR 발 에 따른 강직성 척추염 활액막세포에서 증가하

는 싸이토카인 변화를 찰한다.

방법: 강직성 척추염 환자의 무릎에서 활액막 세포를 추출하여 배양하고, 조군으로 퇴행성 염 환자의 무릎에서

추출한 활액막 세포를 배양하여 비교군으로 선정한 후 각각의 세포에서 TLR(TLR1-9)의 발 을 flow cytometry로 확인한

다. 이후 확인된 TLR에서 TLR을 자극하는 물질을 처리하여 TLR의 발 을 증폭시키고, 각각의 활액막 세포에서 증가되는

싸이토카인을 찰한 후 분석한다.

결과: 강직성 척추염 활액막 세포에서는 TLR2와 TLR4의 발 이 증가되었으나, 퇴행성 염 활액막 세포에서는 발 되

지 않았다. TLR2와 TLR4가 발 된 강직성 척추염의 활액막 세포에 LPS를 처리한 결과 NF-κB를 통한 IL-6와 TNF-α의

증가를 찰하 다.

결론: 강직성 척추염의 활액막 세포에는 TLR2와 TLR4가 발 되며, 활액막 세포에서 NF-κB를 통하여 TNF-α와 IL-6

의 증가가 이루어진다. 따라서 강직성 척추염의 활액막 세포에 있는 TLR2와 TLR4의 발 을 억제하는 방법이 강직성

척추염 치료의 한가지 방법일 것으로 추정한다.


S235

The Impact of Thyroid Autoimmunity on Arterial Stiffness in Postmenopausal Female Patients with Fibromyalgia


이홍직ㆍ이지

Objective: The exact mechanism of the arterial stiffness in fibromyalgia (FM) remains unclear. The present study aimed to

evaluate the association between thyroid function and markers of arterial function in postmenopausal female FM patients.

Methods: This study included 163 postmenopausal female FM patients without any known cardiovascular diseases and within

a normal reference range of thyroid-stimulating hormone (TSH) level. Clinical parameters including the Fibromyalgia Impact

Questionnaire (FIQ), the pain visual analogical scale (VAS) and tender point counts were measured. Vascular function was as-

sessed by brachial-ankle pulse wave velocity (baPWV) and flow-mediated dilation (FMD). We evaluated the associations between

arterial markers and serum TSH, free thyroxin, as well as serum thyroidperoxidase autoantibody (TPO Ab).

Results: Patients with a high baPWV (≥1,490 cm/s) showed more positive TPO Ab (65% vs. 10%, P=0.006) than those with

a normal baPWV. Additionally, the baPWV values of patients with positive TPO Ab were significantly different from those

with negative TPO Ab. Age, FIQ and TPO Ab were significantly correlated with baPWV and FMD (all P＜0.05). Multiple

linear regression analysis revealed that the only significant predictors of baPWV were age, FIQ, and the presence of TPO Ab

after adjustment for traditional risk factors. A significant association was also found between FMD and positive TPO Ab.

Conclusion: Age, functional status, and presence of TPO Ab were significantly associated with increased arterial stiffness in

postmenopausal female FM patients. Given the combined thyroid autoimmunity in FM patients, a re-evaluation of the effects

on the vasculature may be necessary.


S236

Smart App for Diagnosing and Evaluating of Activity of Rheumatic Diseases

Department of Internal Medicine, Wallace Memorial Baptist Hospital1, Dong-A Medical Center2, Gim-hae Samsung Hospital3, Korea

Choong Won Lee1, Sung Won Lee2, Hyun Sung Lee3

Objective: Several classifications or diagnostic criteria were introduced to provide the assessment of rheumatic diseases. A num-

ber of methods were also introduced to evaluate the activity of the disease. However it is not always convenient these to the

patient in clinic and hospital bedside setting. We developed an application for the iPad to diagnosis rheumatic disease and evaluate

the activity.

Methods: We have collected the classification and diagnostic criteria as well as methods to evaluate the activity of rheumatic

diseases that were approved by ACR, EULAR, WOMAC, SLICC, ASASS, PRINTO, and PRES. Application program is applied

with Xcode 4.5 for iOS. The program has a tabbed interface with the following three functions. 1) Classification and diagnosis:

this is to apply the mentioned diagnostic and classification methods to diagnose 26 types of rheumatic diseases. 2) Diseases

activity: This is the function to apply the methods to evaluate the disease activity and/or the remission of 9 types of rheumatic

diseases. 3) Treatment: This tab contains the guidelines and recommendations on the management of 9 types of rheumatic diseases.

Results: It is a very useful smart App to provide guideline for the diagnosis of rheumatic diseases and evaluation of disease

activity for patients with rheumatic disease. This App has been proven useful by both rheumatologist and general practitioner.


S237

통풍환자에서 생긴 다발성 무 성 골두 괴사

원 학교 의과 학 내과학교실

하명수ㆍ오수진ㆍ김송이ㆍ이창훈ㆍ이명수

서론: 통풍은 요산 결정이 에 침착하여 생기는 염증성 염으로 주로 소수 을 침범한다. 무형성 골두 괴사는

색 골 내 압력 증가로 인한 골괴사로 외상, 스테로이드 투여, 음주, 만성 신질환 통풍과 련이 있다. 자들

은 은 여성 통풍 환자에서 양쪽 퇴 골두 왼쪽 상완 골두 괴사를 진단하여 인공 치환술을 시행하 기에 보고하

는 바이다.

증례: 양손의 1∼5번째 근 지간 에 통풍 결 로 보이는 다발성 흰색결 과 내원 2개월 부터 심해진 왼쪽 어깨

통증을 주소로 내원한 31세 여자환자로 2010년 양측 퇴 무 성 골두 괴사로 인공 치환술을 실시한 기왕력이 있었

다. 환자는 외래에서 콜킨, 소염진통제, 알로푸리놀을 투여하며 간헐 인 통풍발작이 있던 분으로 2010년부터 왼쪽 어깨

굴곡 외회 시 통증 지속되어 Dual Energy CT에서 왼쪽 어깨 내 요산결정 침착 확인되었으며 내원 2개월 부터

어깨 통증 심하여 MRI 실시 결과 좌완 무 성 골두 괴사로 진단되어 인공 삽입술을 시행하 다.

결론: 통풍은 동반질환으로 고 압, 당뇨, 고지질 증 신장질환을 일으킬 수 있으며 드물게 무 성 골두 괴사를 일으킬

수 있으므로 세심한 찰이 필요할 것으로 생각된다.


S238

귀안의 염증성 용종으로 처음 확인되었던 통풍성 결 의 1

서울 학교 의과 학 내과학교실1, 서울 학교 의과 학 이비인후과교실2

윤명재1ㆍ오혜진1ㆍ구본승1ㆍ이 호2ㆍ이은 1

통풍은 고요산 증과 그로 인해서 요산 결정이 연부조직에 침착하여 염증 통증을 일으킬 수 있는 질환이다.

일반 으로는 요산 결 이 부 에 침착하여 통증을 일으키는 경우가 흔하며, 신장이나 요로계에 침범하여 요로

결석을 일으키는 경우가 있다. 그러나 이러한 형 인 부 외에 피부나, 얼굴부 를 침범하는 경우도 드물게 있다.

증례: 6년 부터 통풍으로 추정되는 반복 인 발가락 수골의 염을 겪어왔던 67세 여자 환자로 귀안의 답답한 증상

과 통증, 귀에서 나오는 이분비물의 소견으로 이비인후과 진료후 고막근처 외이도부 의 염증성 용종으로 진단되어 치료

이었다. 외래에서 시행한 처음의 조직 검사에서는 육아종성 조직의 소견만이 확인되었다. 그러나 입원해서 귀안의

용종을 제거하는 수술을 시행하 고, 수술후 조직검사에서 통풍의 crystal 소견이 확인되었다. 이후 환자는 항생제와 함께

통풍에 한 치료를 시작하 고, 증상의 호 을 보 다.

통풍 결 은 인체내 다양한 부 에 침착하여 증상을 일으킬 수 있으나, 귀속을 침범하는 경우가 흔하지는 않다. 외국의

경우 귀안에 통풍결 이 발견된 증례가 있었다. 국내에서 귀안의 염증성 용종으로 처음 확인되었던 통풍성 결 의 사례가

있어서 보고하는 바이다.


S239

일차성 부갑상선 기능항진증으로 인한 칼슘피로인산 결정침착 질환 1

한양 학교 류마티스병원 류마티스내과1, 한양 학교 류마티스병원 상의학과2, 한양 학교병원 내과3, 햔양 병원 병리과4, 한양 병원 이비인후-두경부외과5, 유태석내과6

손창남1ㆍ김 담1ㆍ주경빈2ㆍ이승훈2ㆍ이지 3ㆍ김동선3ㆍ송 수4ㆍ태 경5ㆍ유태석6ㆍ 재범1

Calcium pyrophosphate dihydrate (CPPD) deposition disease is a heterogeneous group of diseases with CPPD crystal deposition.

Aging is the most common risk factor for CPPD deposition followed by osteoarthritis and previous injury. Occasionally, CPPD

deposition are associated with familial predisposition and metabolic diseases, including hemochromatosis, primary hyper-

parathyroidism, hypophosphatemia, and hypomagnesia. We report a case of a relatively young female patient with CPPD deposi-

tion disease associated with primary hyperparathyroidism, which was diagnosed through polarized microscopic examination of

the synovial fluid and a subtotal parathyroidectomy. A 47-year-old woman was admitted with a 6 day history of right knee

pain and swelling. The patient had intermittently taken NSAID and intra-articular steroid injections because of recurrent knee

pain and swelling over the past 10 years. Physical examination showed pain, swelling, and limited motion in the right knee

joint. Laboratory analysis revealed elevated ESR (77 mm/hr), CRP (8.9 mg/mL), total serum calcium (12.2 mg/dL) level, and

the intact parathyroid hormone (129.1 pg/mL) level, and the serum phosphate (2.3 mg/dL) level was decreased. Rheumatoid

factor, anti-CCP, and HLA-B27 were all negative. X-ray examination showed chondrocalcinosis within the joint space of both

knees and the pelvic joints. Intracellular CPPD crystals were observed in aspirated synovial fluid under polarized light microscopy.

No other features suggesting the presence of primary hyperparathyroidism in the neck US, CT, and 99mTc sestamibi scan were

found. Her knee pain and swelling resolved after the intra-articular injection of triamcinolone. Subtotal parathyroidectomy was

performed to diagnose and treat the primary hyperparathyroidism. The parathyroid specimen showed chief cell hyperplasia of

parathyroid gland. The level of intact parathyroid hormone and serum calcium decreased, following the operation. Physicians

should be aware that primary hyperparathyroidism is one of the causes of CPPD, especially in the young.


S240

A Case of Atypical Femur Fracture in a Patient with RA with Long-term Bisphosphonate Therapy

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases1, Department of Internal Medicine, Hanyang University Hospital2, Department of Radiology, Hanyang University Hospital for Rheumatic

Diseases3, Department of Orthopaedic Surgery, Hanyang University Hospital4, Korea

Chang-Nam Son1,2, Sodam Jung2, Dam Kim1,2, Ji-Young Choi1,2, Seunghun Lee3, Yi-Suk Kim4, Yoon-Kyoung Sung1,2

Introduction: Atypical femur fracture is a fracture featured with subtrochanteric or diaphyseal location, transverse fracture line,

and paucity of trauma. It is associated with vitamine D deficiency, rheumatoid arthritis (RA), hypophosphasia, and use of certain

drugs such as glucocorticoid and proton pump inhibitor. Recently, enormous studies have been reported that the risk of atypical

femur fracture could be increased with long-term bisphosphonate treatment. We report a case of atypical subtrochanteric femur

fracture in a patient with RA treated with bisphosphonate.

Case Report: A 60-year-old woman was admitted with four months history of left hip pain. She had been diagnosed with

RA and osteoporosis 5 years previously. She had been treated with methotrexate, leflunomide, prednisolone, and celecoxib for

RA and alendronate for osteoporosis over the past 5 years. On physical examination, there was severe tenderness on the left

inguinal area but no evidence for active arthritis. Radiologic examination showed transverse fracture line in the subtrochanteric

area of left femur without angulation. Whole body bone scan showed oblique linear uptake and MRI showed insufficiency fracture

with adjacent bone marrow edema in the proximal left femur. No other features within the pelvic joint in all x-ray, bone scan,

and MRI were observed. With comparable radiologic findings and no history of high energy trauma, she had been diagnosed

as atypical femur fracture with bisphosphonate use. Her laboratory data showed that bone turnover markers decreased with alkaline

phosphatase 42 U/L (reference range 30∼110 U/L), osteocalcin 4.1 ng/mL (reference range 13∼48 ng/mL), and serum C-telopep-

tide 0.15 ng/mL (reference range 0.556∼1.008 ng/mL). She underwent closed reduction and surgical internal fixation.

Conclusion: Atypical femur fracture might be one of differential diagnosis of hip pain in RA patient, especially in the patient

who have treated with bisphosphonate.


S241

셀 콕시 사용 후 발생한 Sweet 신드롬의 증례1

한양 학교 의과 학 내과학교실1, 한양 학교부속병원 류마티스병원2, 한양 학교 의과 학 피부과학교실3, 한양 학교 의과 학 병리학교실4

정소담1ㆍ이지 2ㆍ김 담1ㆍ손창남2ㆍ고주연3ㆍ박찬 4ㆍ유 1

서론: Sweet증후군은 발열, 호 구성 백 구 증가증을 동반한 압통성 을 보이면서 상부 진피에 주로 호 구로 구성된

염증세포의 침윤과 부종을 특징으로 한다. 상기도 감염, 염증성 장 질환, 임신 후에 형 인 Sweet 증후군이 발생할

수 있으며, 악성종양이나 약물에 의해서도 발생할 수 있다. 자들은 셀 콕시 사용 후 나타난 Sweet 증후군 환자를

경험하여 이를 보고하고자 한다.

증례: 내원 7개월 발생한 상, 하지의 피부발진을 주소로 내원한 58세 여자 환자로 2년 천식과 류마티스 염을

진단받고 약물복용 이었다. 타원에서 시행한 피부 조직검사에서 염증 소견으로 항생제 치료를 하 으나 호 이 없었으

며, 왼쪽 발목 부 는 피부괴사로 이식수술을 받았다. 항류마티스제는 단한 상태 으며 객담 검사에서 M. avium 양성으

로 피부결핵 의심 하에 항결핵제를 투여 이었다. 상, 하지에 통증을 동반한 붉은 반 양상의 경계가 명확한 피부발진이

다발성으로 나타났으며, 두세 개의 반 이 하나로 합쳐지는 양상으로 일부는 물집 고름집을 포함하고 있었다. 재원

병변이 심해지면서 발열이 나타났고, 시행한 검사에서 CRP 11.1 mg/dL ESR 100 mm/hour, 왼쪽 발바닥의 피부 생검에

서 진피 상층에 다량의 호 구가 호산구와 함께 침윤된 소견으로 Sweet 증후군을 진단하 다. 기타 약제를 단하고

드니솔론 30 mg을 매일 투여하면서 피부 병변 발열, 통은 하게 호 되었다. Sweet 증후군을 일으키는

원인 하나인 셀 콕시 를 피부 병변 발생 에 사용했고 단 이후 잠시 호 되었던 과거력 재원 잠시 사용했던

시기에 증상이 심해졌던 것으로 볼 때 연 성이 있다고 사료되나, 재투여로 확인하지는 못하 다. 이후 증상 조 되고

다른 합병증 없어 퇴원하고 외래 추 찰 이다.

결론: 염 환자에서 셀 콕시 는 매우 흔하게 사용되고 있으나 그로 인해 발생한 Sweet 증후군의 국내 보고는 없는

상황이다. 따라서 셀 콕시 사용 후 발열 통증을 동반한 경계가 명확하며 물집 고름집을 포함하는 발진이 발생하

는 경우 Sweet 증후군을 고려할 필요가 있다고 사료되어 보고하는 바이다.


S242

류마티스 염 환자에서 종양괴사인자 억제제 사용 발생한 미만성 폐포 출 1

순천향 학교 서울병원 내과학교실1, 조선 학교병원 내과학교실2

김혜진1ㆍ조홍성2ㆍ김윤성2ㆍ김 숙1

종양괴사인자 억제제는 자가면역질환, 특히 류마티스 염(Rheumatoid arthritis, RA)과 강직성 척추염에서 폭넓게 쓰이

며 표 인 부작용은 결핵 기회감염의 증가이다. 미만성 폐포 출 은 감염 없이 폐의 소 에서 폐포내로 출 을

일으켜 호흡곤란 산소증을 일으키고 양폐야에서 범 한 침윤을 일으켜 사망률을 높히는 주의를 요하는 합병증이

다. 이를 일으키는 주요 원인으로는 면역학 원인 이외에 약물에 의한 직 독성 등의 원인이 있으나 아직까지 adalimu-

mab에 의한 미만성 폐포 출 의 보고는 없다. 자들은 RA 치료로 종양괴사인자 억제제 하나인 adalimumab 투여

미만성 폐포 출 이 생긴 증례를 경험하 기에 문헌고찰과 함께 증례 보고하는 바이다. 69세 여자로 호흡곤란을 주소

로 내원하 다. RA 치료를 해adallimumab을 투여 9개월 에 생긴 DAH로 입원 후 호흡곤란이 악화되고 기 내 삽 을

시행하고 면역 하 상태의 폐렴에 하여 Ceftazidime, Levofloxacin 의 항생제를 투여하 다. 입원 2일째, 오래된 액빛

(old blood clot) 양상의 가래가 지속 으로 흡인되어 기 지 내시경을 시행하 다. 폐포 세척액 배양검사에서 세균이나

진균은 보이지 않았다. 기 지폐포 세척액에서 헤모시데린 풍부한 식세포(hemosiderin-laden macrophage)가 찰되어

확진되었다. 종양괴사인자 억제제의 RA 치료 효과는 언 할 필요도 없이 우수하다. 그러나 임상에서 사용시 나타날 수

있는 심각한 부작용을 고려하고 써야 하며 특히 고령, 기 폐질환 액 응고 결핍을 일으킬 수 있는 약제를 복용하고

있는 경우는 DAH 한 염두에 두어야겠다.


S243

류마티스 염 환자에서 발생한 치아돌기 비외상골

울산 학교 의과 학 서울아산병원 류마티스내과학교실

배승 ㆍ김용길ㆍ신명진ㆍ 상용ㆍ윤다림ㆍ홍석찬ㆍ김유재ㆍ구본산ㆍ이창근ㆍ유 빈

서론: 류마티스 염은 만성 이고 칭 인 손발 염과 골미란을 특징으로 하는 질환으로 1, 2번 경추의 불완 탈구

(subluxation)가 질병 기에도 나타날 수 있으며 유병률이 25∼80%까지로 보고되고 있다. 1, 2번 경추의 불완 탈구 시

환자가 호소하는 증상은 목통증이 부분이고 염증의 징후가 겉으로 나타나지 않기 때문에 심각성을 간과할 수 있으나

골 이 발생하는 경우 환자에게 치명 인 합병증을 가져올 수 있다. 자들은 외상의 과거력 없이 발생한 2번 경추 치아돌

기 골 로 인한 손발 감각 하 증상으로 내원하여 류마티스 염을 진단한 1 를 경험하여 보고하는 바이다.

증례: 외상의 과거력이 없는 77세 여자가 내원 한달 부터 심해진 손, 발 감각 하 림 증상으로 내원하 다. 경추

CT검사에서 2번 경추 치아돌기 골 확인되었고 자기공명 상에서 치아돌기 골 에 의한 척수 압박 소견이 확인되었다.

환자 내원 당시 의 성 염증 소견 보이지는 않았으나 구 침강속도 51 mm/hr (정상＜20)로 상승되어 있었으며

C-반응단백은 0.23 mg/dL (정상＜0.6)로 찰되었다. 한 류마티스인자는(RF) ＜10.6 IU/mL로 음성이었으나 Anti-CCP

Ab ＞340 U/mL로 강양성 확인되었으며 양손 x-ray에서는 체 으로 주변 골감소 소견과 오른손 4번째 근 지

(PIP) 왼손 5번째 무지 수지 (MCP)에서 골미란 강 착 소견 동반되어 있었다. 소견을 근거로 2010

ACR/EULAR 진단기 을 만족하여 류마티스 염으로 진단할 수 있었다. 본 증례는 류마티스 염 환자에서 외상없이

2번 경추 치아돌기 골 이 발생한 경우로 유병기간이나 질병 활성도에 계없이 1, 2번 경추 불완 탈구 여부에 한

확인이 반드시 필요하다는 을 시사해 다.


S244

A Case of Renal AA Amyloidosis and Chronic Kidney Disease in Patient with Rheumatoid Arthritis with a Good Response to Etanercept

Divison of Nephrology, Department of Internal Medicine, Jeju National University, School of Medicine1, Divison of Rheumatology, Department of Internal Medicine, Jeju National University, School of Medicine2, Korea

Hyun Woo Kim1, Jung Won Noh

2, Jinseok Kim

2

Secondary amyloidosis is one of most severe complication of rheumatoid arthritis (RA) for which no effective treatment has

been demonstrated. Although the benefits of tumor necrosis factor alpha inhibitors in RA is well known, their role in renal

amyloidosis secondary to RA is unclear and their safety in patients with chronic kidney disease has not been well reported.

We report a case of renal AA amyloidosis in patient with RA, who responsed well to etanercept. At the age of 65, the patient

developed gravitational edema, overt proteinuria and moderate renal failure 6 years after diagnosis of RA, who was treated with

methotrexate, hydroxychlorquine, leflunomide and low dose steroid. Renal biopsy revealed 41 glomeruli, 21 with global sclerosis

(51%), eosinophilic material deposition in mesangial matrix and capillary loop and patchy areas of interstitial fibrosis. The deposits

tested positive for Congo red staining with green birefringence under polarization microscopy and immunohistochemical staining

detected the presence of amyloid A protein. Based on the pathologic findings, she was diagnosed with secondary amyloidosis

associated with refractory rheumatoid arthritis. The patient was treated with etanercept 25 mg, administered as a subcutaneous

injection twice weekly for 8 months, which led to a decrease in proteinuria and stabilization of renal function over time.

Furthermore, the patient had no complications following the treatment.


S245

류마티스 염에서 발병한 성 신부 다발성 골수종 증례

아주 학교 의과 학 류마티스내과학교실1, 종양 액내과학교실2

황선 1ㆍ배창범1ㆍ정주양1ㆍ김 아1ㆍ정성 2ㆍ서창희1

서론: 자가면역질환에서 림 증식성 질환의 발생이 증가되는 것으로 알려져 있지만 그 유병율은 매우 낮다. 따라서 류마

티스 염(Rheumatoid arthritis, RA)에서 림 증식성 질환이 동반되는 경우는 매우 드물게 보고되는데, RA환자가 성

신부 으로 내원하여 다발성 골수종을 진단받은 바 있어 이를 보고하고자 한다.

증례: 66세 여환은 내원 1개월 시작된 신 쇠약감을 주소로 내원하 다. 환자는 4년 RA를 진단받고 치료받던

3년 자의로 치료를 단하 고 3개월 통이 악화되어 다시 내원하여 약물치료를 시작하 다. 당시 액

검사에서는 류마티스인자가 45 U/ml으로 상승된 것 외에 모두 정상 소견이 고 조조강직과 통이 지속되어 hydroxy-

chloroquine, methotrexate, leflunomide, NSAID를 유지하던 이 다. 내원 당시 약 6시간동안 지속되는 조조강직과 양측

근 지 의 압통과 종창, 양측 견 , 슬 에 압통이 있었다. 말 액 검사상 백 구 8,300/uL, 색소 11.0 g/dL,

구용 률 32.6%, 소 201,000/uL, 구 침강 속도 37 mm/hr, C-반응 단백 0.39 mg/dL, 청 총 단백 6.7 g/dL,

알부민 4.3 g/dL, Alkaline phosphatase 115 IU/L, ALT 52 IU/L, AST 51 IU/L, BUN 35.9 mg/dL, 크 아티닌 5.3 mg/dL이 고

소변검사에서 단백뇨 1+, 단백/크 아티닌 비율이 4.78 g로 측정되었다. 성신부 의 원인을 밝히기 한 검사들을 시행

하 고, 청 기 동 검사와 면역 기 동검사, 요단백 기 동 검사에서 kappa형의 단일클론성 단백이 찰되었으며

신장 조직 검사에서 cast nephropathy를 보 고 골수 흡인 검사에서 형질세포가 70%로 증가되어 있었다. 환자는 kappa형의

병기 IIIB 다발성 골수종으로 진단되어 항암화학요법을 시행받았고 RA의 치료를 하여 hydroxychloroquine 300 mg, bu-

cillamine 200 mg, prednisolone 10 mg을 유지하여 퇴원하 다.

고찰: RA에서의 B 림 구의 증식과 면역 로불린의 증가가 다발성 골수종의 발병기 과 공통 을 보이고림 증식성

질환으로 진행하는데 취약한 CD5 양성 B 림 구가 보고되어, RA에서 림 증식성 질환의 발병과의 연 성을 뒷받침하고

있다. 따라서 RA환자에서 진행하는 단백뇨 성신부 을 보일 경우 단백 기 동과 신장조직검사 등의 검사들이

필요하며, 다발성 골수종의 가능성을 고려해보아야 하겠다.


S246

A Case of Renal Lupus Vasculitis with Pauci-immune Glomerulonephritis in Patient with Systemic Lupus Erythematosus

Divison of Rheumatology, Department of Internal Medicine, Jeju National University, School of Medicine1, Department of Internal Medicine, Jeju National University, School of Medicine2, Korea

Eun-Jung Park1, Sung Hyun Kim

2, Jinseok Kim

1

Renal lupus vasculitis is one of the rare vascular lesions complicated with systemic lupus erythematosus (SLE), and is often

overlooked in the actual renal biopsy specimen. We report a case of biopsy-proven renal lupus vasculitis with pauci-immune

glomerulonephritis in patient with SLE. She was diagnosed with SLE at the age of 16, and was treated with prednisolone, hydroxy-

chloroquine, and methotraxate. The patient had a history of aortic stent insertion for abdominal aortic dissection related to newly

diagnosed Marfan’s syndrome during follow-up period. At the age of 29, she developed hematuria and overt proteinuria and

admitted to perform a kidney biopsy. Laboratory finding revealed reduced serum C3, C4 and increased anti-ds DNA antibody

titer. Antiphospholipid antibodies and ANCA were negative and complete blood count was unremarkable. Renal biopsy revealed

29 glomeruli with increased mesangial cell number, ischemic wrinkling, and segmental loop necrosis with fibrin deposition.

Additionally, interlobular arteries and afferent arterioles frequently demonstrated severe necrosis with fibrin deposition, focally

occluding the lumen. Immunofluorescent and electron microscopy revealed no electron-dense and immune deposits in glomeruli

contrast to those in vascular wall which present IgG, IgM and IgA, indicating a full-house pattern, and C3 and C1q deposition.

Based on the pathologic findings, renal lupus vasculitis with pauci-immune glomerulonephritis was suspected. The patient was

treated with monthly intravenous cyclophosphamide pulses and high dose steroid, showing good response on further follow-up.

This case represents renal lupus vasculitis with or without lupus nephritis should be considered in lupus patient with proteinuria,

and cyclophosphamide could be a treatment of choice.


S247

신홍반루푸스 환자에서 발생한 피막성 경화복막염 1

인제 학교 의과 학 일산백병원 내과학교실1, 서울백병원 내과학교실2

배상철1ㆍ이주 1ㆍ김유선2ㆍ나종천2ㆍ윤보 1

배경: 피막성 경화복막염은 복막의 섬유화와 유착을 특징으로 하는 질병으로, 치료하지 않을 경우 장폐색이나 장피 공

등이 발생할 수 있는 질환이다. 복막투석을 시행 인 환자에서 드물게 발생하며, 신성 자가면역질환, 장 질환,

복막과 복강내 악성종양과 동반되는 가 보고된 바 있다. 본 자들은 과거 병력이 없는 은 남자에서 신홍반루푸스

와 동반된 피막성 경화복막염 1 를 경험하여 문헌고찰과 함께 보고하는 바이다.

증례: 과거병력이 없는 22세 남자가 내원 1개월 부터 시작된 왼쪽 상복부의 팽만감과, 진행하는 양상의 복통으로

입원하 다. 복부 진찰시 장음의 감소 소견과 함께, 이동 둔탁음 반 인 압통이 찰되었으며, 흉부청진에서 양쪽

폐하부의 호흡음이 감소되어 있었으며 흉골 좌연 하부에서 이완기에 발생하며, 심첨부에서 수축기에 발생하는 2도의

심잡음이 청진되었다. 이학 검사 결과, 구침강속도는 44 mm/hr C-반응단백은 0.7 mg/dL, 항핵 항체 양성

(speckled pattern, 1：1,280) 항 dsDNA 항체가 양성 소견이었으며, 청 complement 3 (C3)와 complement 4 (C4)는 각각

60 mg/dL (90∼180 mg/dL)과 9 mg/dL (10∼40 mg/dL)로 감소되어 있었다. 환자는 신홍반루푸스 (구강 궤양, 장막염,

항 dsDNA 양성, 항핵 항체 양성)에 동반된 루푸스 복막염 (lupus peritonits)으로 진단 후, Methylpredisolone 1,000 mg×3일

간 정주 치료하 으며, 이후 Prednisolone 1 mg/kg 정주 치료 유지하 다. 입원 1주일 후 임상 양상의 호 없이 여 히

복통을 동반한 장마비 소견 지속되어, 고용량 면역 로불린 정주 치료 (400 mg/kg×5 days)를 시행하 으나, 증상의 호

없어 입원 21일째에 복강경을 통한 복막조직검사를 시행하 고, 피막성 경화 복막염으로 확진되었다. 본 자들을 성

염증성 병변에 한 치료로 Cyclophosphamide 정주 치료 후, 후복강 내 유착 박리술을 시행하기로 계획하 다. 입원 30일

째 1차 cyclophosphamide 정주 치료를 시행하 으며, 입원 43일째에 장 출 이 발생하여, 내시경을 통한 지 치료

구 수 을 시행하 으나, 출 의 지속 심장 기능의 부 으로 인한 폐부종 악화 소견으로 사망하게 되었다.


S248

Acute Inflammatory Demyelinating Polyradiculoneuropathy in Patient with Systemic Lupus Erythematosus


Jeong-Won Lee, Dong-Jin Park, Kyung-Eun Lee, Ji Hyoun Kang, Lihui Wen, Tae-Jong Kim, Yong-Wook Park, Shin-Seok Lee

Neuropsychiatric manifestations in systemic lupus erythematosus (SLE) are ranged from 37∼95%. Among 19 neuropsychiatric

manifestations, acute inflammatory demyelinating polyradiculoneuropathy (AIDP) is quite rare and is characterized by progressive,

symmetric muscle weakness accompanied by absent or depressed deep tendon reflexes. Generally, plasma exchange and intra-

venous immunoglobulin are main treatment modalities in these patients. Here, we report a case of AIDP in a 29-year-old SLE

patient who was fully recovered with treatment of high-dose glucocorticoid and immunosuppressive agents. The patient was admit-

ted with 2-week history of quadriparesis. She was diagnosed as having SLE 5 years ago based on malar rash, lymphopenia,

and positive antinuclear and anti-dsDNA antibodies. She stopped her medication 17 months ago due to no disease activity. She

had progressive symmetric motor weakness in both upper and lower extremities which started from proximal and progressed

to distal part of the extremities. Biceps/triceps tendon reflex was decreased and patellar/ankle tendon reflex was absent. AIDP

was diagnosed based on nerve conduction study which showed absent both F waves and H reflex in upper extremities. Cell

counts of cerebrospinal fluid were normal and antibody against ganglioside was negative. After treatment with high dose cortico-

steroid and cyclophosphamide pulse therapy, symptoms started to improve after 2 weeks and she was fully recovered after sub-

sequent courses of pulse cyclophosphamide. This case suggests that AIDP should be treated differently in SLE patients and clini-

cians should keep in mind these specific aspects in treating SLE patients.


S249

루푸스 환자에서 스테로이드 충격 요법 후 발생한 폐출 에서 Rituximab을 이용한 치료 1


임상우ㆍ이상엽ㆍ이성원ㆍ정원태

25세 여자 환자가 pancytopenia로 루푸스를 처음 진단 받은 후 심한 용 성 빈 과 소 감소증으로 스테로이드 충격

요법(metylprednisolon 1g×3 days) 후 prednisolone 60 mg으로 바꾸고 나서 3일 뒤 갑자기 심한 객 과 호흡 곤란을 호소하

다. 이에 시행한 흉부 촬 상 양측 폐하에 출 소견을 보 다. 이에 자들은 다시 3일간 스테로이드 충격 요법

(methylprednisolon 1 g×3 days)과 Rituximab (1,000 mg×2 weeks) 를 이용하여 루푸스에 동반된 폐출 을 치료하 다. 이후

환자는 스테로이드를 서서히 으며 외래에서 치료 이다.


S250

신홍반루푸스 환자에서 Cyclophosphamide Pulse 치료 후 발생한 스트 스 유발성 심근증 1

경희 학교 의과 학 내과학교실

이유호ㆍ송 란ㆍ이상훈ㆍ이연아ㆍ홍승재ㆍ양형인

배경: 신홍반루푸스는 면역복합체가 , 조직에 침착하여 발생하는 자가면역 질환이며, 증도의 신홍반루푸스에

서는 고용량의 스테로이드와 cyclophosphamide를 투여하게 된다. Cyclophosphamide에 의한 심장 독성은 주로 골수이식을

계획 인 환자에게 고용량의 cyclophosphamide를 투여 하 을 때 발생하는 것으로 알려져 있다. cyclophosphamide에 의한

스트 스 유발성 심근증(stress induced cardiomyopathy)는 매우 드물게 보고되고 있으며 국내에는 보고된 바가 없다. 이에

자들은 루푸스신장염 환자에게 고용량의 cyclophosphamide를 투여한 후 스트 스 유발성 심근증이 발생한 증례를 보고

하고자 한다.

증례: 33세 여자가 1개월 부터 시작된 신 부종을 주소로 내원하 다. 환자는 12년 신홍반루푸스를 진단 받고

약물 치료를 받았으나 1년 3개월 임신을 하면서 약물을 임의로 단하고 지내던 이었다. 내원 당시 액 검사에서

항이 가닥DNA 항체 ＞300 IU/mL, C3/C4 29/3 mg/dL, ESR 42 mm/h, CRP 0.93 mg/dL, BUN/Cr 40/2.2 mg/dL, 소변 검사에서

blood 3+, protein 3+ 소견을 보여 신장 조직검사를 시행하 고, 루푸스신장염 class IV 을 진단받았다. 한 흉부 X선 검사에

서 심장비 가 찰되어 심 음 를 시행하 고, 증도의 심낭 삼출과 폐동맥 고 압 (폐동맥압 66 mmHg) 소견을 확인하

다. 루푸스신장염에 한 치료로 3일간의 정주 메틸 드니솔론 500 mg/일, cyclophosphamide 500 mg/일을 투여하 고,

폐동맥고 압에 해 tracleer를 추가한 뒤 퇴원하 다. 3주 후 외래에서 cyclophosphamide 500mg/일을 재 투여 하 고, 당일

새벽 실신을 주소로 응 실을 통해 입원하 다. 입원 후 시행한 심 음 에서 폐동맥 고 압의 악화(폐동맥압 91 mmHg)

스트 스 유발성 심근증 혹은 상동맥의 좌 하행 분지의 허 (좌심실 박출계수 33%)이 의심되는 소견을 보여 심

조 술을 시행하 고 상동맥의 이상은 찰되지 않아 스트 스 유발성 심근증을 진단하 다. 메틸 드니솔론 125

mg/일 투여 보존 인 치료를 하 으나 환자는 치료 2일째에 원인이 명확하지 않은 심정지가 발생, 사망하 다.


S251

쇼그 증후군 환자에서 흉선과 폐를 침범한 MALT림 종 1

서울 학교 의과 학 내과학교실1, 병리학교실2

오혜진1ㆍ윤명재1ㆍ구본승1ㆍ이상진1ㆍ김경록1ㆍ 윤경2ㆍ송 욱1

흉선과 폐를 침범한 MALT 림 종은 매우 드문 질환이지만, 쇼그 증후군에서 림 종의 발생 빈도가 일반인에 비해

16배에서 44배까지 증가되어 있고, 증례에서 흉선암으로 의심했던 병변이 MALT 림 종으로 확진 되었다는 에서 쇼그

증후군 환자에서 림 종의 발생에 한 주지와 찰이 요하다. 쇼그 증후군은 안구와 구강의 건조증을 래하는

자가면역 질환으로 약 5%에서 악성 림 종이 동반하는 것으로 알려져 있다. 문헌에 의하면 특히 Mucosa-Associated

Lymphoid Tissue (MALT) 림 종이 쇼그 증후군 환자에서 발생하는 비호지킨림 종의 약 44%를 차지하고 있다. 한,

쇼그 증후군 환자에서 MALT 림 종은 침샘에서 가장 흔히 발생한다고 알려져 있다. 최근 자들은 쇼그 증후군

환자에서 흉선과 폐를 동시에 침범한 MALT림 종을 경험하여 보고하고자 한다. 약 7년 에 쇼그 증후군으로 진단받

은 50세 여자로 타병원에서 간헐 으로 약물 치료를 받던 에 약 2∼3개월 부터 악화된 다발성 통을 주소로 내원

하 다. 구강과 안구의 건조증이 있었고, 기침 흉골하 부 의 통증을 호소하 다. 흉부 컴퓨터 단층 촬 에서 종격동의

앞쪽에 약 3.4 cm 크기의 흉선 결 과 양측 폐의 하부에 망상 결 성 음 증가가 발견되어 기 지 내시경 기 지

음 유도 하 조직검사를 시행하여, 폐 조직의 림 구 침윤이 찰되었고 종양 세포는 발견되지 않았다. 침습성흉선암

을 의심하여 흉선 폐의 제술을 시행하 으나, 병리 소견에서 흉선과 폐의thymic extra-nodal marginal zone B cell

lymphoma of MALT에 합당한 소견이 찰되었다. 쇼그 증후군 환자에서 흉선과 폐를 동시에 침범한 MALT 림 종은

매우 드물게 발생하여 문헌 고찰과 함께 보고하는 바이다.


S252

Primary Sjögren's Syndrome in Identical Twin

Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine of Chonbuk National University Hospital-Chonbuk National University, Korea

Yu-Ji Kim, Yun-Jung Choi, Ha-Yong Yoon, Won Seok Lee, Wan-Hee Yoo

Sjögren's syndrome (SS) is a chronic autoimmune disorder in which the body's immune system mistakenly attacks exocrine

glands with associated lymphocytic infiltrates of the affected exocrine glands. Genetic predisposition may be implicated in the

cause of SS, and several families involving two or more cases of SS have been reported. Thus, we suspected that monozygotic

twins represented a very similar phenotype with cilinical symptom and similar selorogic data, including anti-Ro/SSA and an-

ti-La/SSB. But, the degree of genetic constribution in primary SS remains to be clarified. A 20-yr-old man patient visited our

hospital with mild dry eye and mouth for several months. There was no facial rash, and no oral ulcer. Laboratory tests showed

anti-Ro/SSA antibody was positive and other autoantibodies to specific antigens were all negative. He performed salivary scan

and reveled mild delayed excretory function in both parotid and submandibular glands compatible with SS. Based on the history,

clinical presentation of the patient and above investigatory findings, a confirmatory diagnosis of primary Sjogren’s syndrome was

given. He was identical twin. His older brother attended our outpatient department, because of possibility of combined rheumatic

disease. He did not have any symtoms, but laboratory studies documented Anti-La/SSB antibody was positive and salivary scan

showed midly decreased secretory and excretory function in both parotid glands. Considering the laboratory features and finding

of salivary scan, clinical diagnosis was appropriate for SS. Herein we report a case of monozygotic twin brothers with primary

SS. Physicians should consider that silbilngs will be monitored carefully for the possibility of SS if a twin sibling has SS.


S253

Pulmonary Nodular Amyloidosis in Patients with Sjögren's Syndrome


In-Suk Min, Yun-jung Choi, Ha-Yong Yoon, Won Seok Lee, Wan-Hee Yoo

Sjögren's syndrome (SS) is a chronic autoimmune disorder characterized by lymphocytic infiltration of exocrine glands resulting

in dry mouth (xerostomia), dry eyes (keratoconjunctivitis sicca), parotid gland enlargement, and the presence of various au-

to-antibodies. SS frequently have pulmonary involvement, such as interstitial lung disease, primary pulmonary lymphoma, and

pleuritis. Amyloid deposition on lung in patients with SS is very rare. We herein report three cases of pulmonary nodular amyloi-

dosis in patients with SS. They are all female and have no respiratory symptoms. They were diagnosed with pulmonary amyloi-

dosis by lung biopsy. (two Video-Assisted Thoracoscopic Surgery, one Percutaneous Transthoracic Fine Needle Biopsy)

Histologically, eosionophilic deposits that were positive for Congo red staining were observed. Radiologic findings showed that

there were multiple pulmonary nodules in two cases and solitary pulmonary nodule in one case. These three cases show that

pulmonary nodular amyloidosis must be considered in the differential diagnosis of the patients with SS presenting with various

pulmonary manifestation.


S254

증 다발성 근염 환자에서 동반된 심장 사르코이드증 1

경북 학교 의과 학 내과학교실

권상훈ㆍ은정수ㆍ김나리ㆍ임철 ㆍ남언정ㆍ강 모

서론: 사르코이드증은 비건락성 육아종성 질환으로 폐문부, 피부, 을 비롯하여 신을 침범하는 질환이다. 아직 그

원인은 명확히 밝 지지 않았으며 자가면역기 이 여하는 것으로 알려져 있다. 사르코이드증에서 심장 침범은 드물게

발생하며 자가면역성 질환과 동반된 증례는 세계 으로 드물다. 특히 다발성 근염이 심근을 침범하는 경우는 가끔 있지만

다발성 근염에 심근 사르코이드증이 동반되는 경우는 보고된 바 없다. 자들은 간질성 폐질환이 동반된 증 다발성

근염환자에서 장기간 추 발견된 우심실 심근 종괴에 해 심장 사르코이드증을 진단한 1 를 경험하 기에 보고하

는 바이다.

증례: 54세 남자 환자가 한 달간 심화된 노작성 호흡곤란을 주소로 내원하 다. 환자는 11년 기침 호흡곤란을

주소로 내원하여 수술 폐 생검 시행 후 간질성 폐질환으로 진단받았다. 이후 근 부 근력 하 증상으로 내원하여 근

도검사 이상과 근육효소 상승으로 다발성 근염으로 진단받았으며, 항 Jo-1 항체검사에 양성이었다. 고용량 스테로이드

경구 cyclophosphamide 치료로 호 되었으며, 이후 azathioprine을 포함한 면역억제 치료로 유지하 다. 내원 후 시행한

HRCT에 폐의 진행된 병변은 없으나, 심장막 삼출액이 찰되었다. 근육효소수치의 증가 근 부 근력 하는 찰되지

않았다. 심장 음 결과 우심실 벽에 73×15 mm 크기의 무반향 종괴 찰되었고, 심장 자기공명 상에도 T2 신호강

도의 동일한 병변이 확인되었다. 심장 양 자방출단층촬 에 18FDG섭취가 국소 으로 뚜렷하게 증가되어 있었다. 심도

자술에 의한 우심실벽 심장조직검사에 비건락성 육아종을 동반한 만성염증성 병변이 있었고 결핵균 검사는 모두 음성으

로 심장 사르코이드증 진단 후 고용량 스테로이드 사이클로스포린, 항 TNF-a 제제로 치료하 다. 추 심장 음

검사상 병변 크기 감소하 으며, 임상증상 호 소견 보여 퇴원하 다.


S255

Asymmetrical Involvement of Lower Leg Muscle, Confused as a Focal Myositis by Infection, in a Dermatomyositis Patient Under Treatment

Department of Internal Medicine, College of Medicine, Hanyang University1, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases2, Korea

황순우1ㆍ이지

1ㆍ정소담

1ㆍ김 담

2ㆍ손창남

2ㆍ유

2

Introduction: Dermatomyositis (DM) is a systemic disease characterized by chronic inflammation in the skin and muscle. This

disease usually induces symmetric proximal muscle weakness and disability. We report a case of DM patient flared with fever,

leg swelling, and asymmetric inflammatory myopathy of distal leg muscles.

Case Report: A 73-year-old woman was admitted with a fever, swelling and weakness of left lower leg. She was diagnosed

to DM three month ago by following evidences; myalgia with weakness, periorbital swelling with rash , shawl sign, Gottron’s

papules at knuckles, increased muscle enzymes, electromyogram showing myopathic triad. Femur MRI also demonstrated in-

flammatory changes at both thigh muscles. Skin biopsy revealed dermatomyositis, but muscle biopsy was not sufficient to make

diagnosis. She was diagnosed to DM, and placed on high dose steroid and methotrexate. She showed improvement of clinical

symptoms with treatment for three months. After modifications of current medications, fever, accompanying weakness, swelling,

and local heat of left lower leg, developed. Laboratory analysis revealed elevated ESR (114 mm/hr), CRP (6.7 mg/dL) level.

On the other hand, CK (241 U/L), LDH (256 U/L) level was not elevated. Under a suspicion of infection, she was treated

with antibiotics and reduction of corticosteroid, but her symptom and laboratory finding did not improve. Left tibia MRI showed

myositis pattern at extensor muscles of left calf. Muscle biopsy showed inflammatory myopathy. Electromyogram of lower ex-

tremities showed acute and chronic myopathic pattern in left lower leg and chronic myopathic pattern only at right leg. Fever,

and left leg swelling resolved after the IVIG, reconstitution of corticosteroid, and addition of cyclosporine. Weakness of left

lower leg was improved, but not completely.

Conclusion: Asymmetrical involvement of DM is very rare. When DM patient has unilateral symptom of extremity, we have

to consider unilateral involvement of DM as a differential diagnosis in addition to focal myopathic conditions including infection.


S256

Dermatomyositis Associated with Gallbladder Cancer


Jin Su Park, Jung Yoon Pyo, Moon Jae Chung, Jung Sik Song, Yong-Beom Park, Soo-Kon Lee, Sang-Won Lee

Dermatomyositis, an idiopathic inflammatory myopathy with characteristic skin manifestations, is associated with several cancer

types. Gallbladder cancer is a rare neoplasm that differs from other high-incidence cancers of the gastrointestinal organs. Only

three cases of gallbladder cancer with dermatomyositis have been reported worldwide and none reported in Korea. We had experi-

enced a case of dermatomyositis accompanied by gallbladder cancer in a patient who had no risk factors for gallbladder cancer.

Only low dose methylprednisolone remained for dermatomyositis. Nevertheless, muscle enzymes, muscle weakness, and skin le-

sions of dermatomyositis were resolved after cancer treatment (5-fluorouracil based concurrent chemo-radiotherapy). We believed

that our case report can emphasize the importance of a malignancy work-up, including for cancers with low incidence, in patients

with an inflammatory myopathy.


S257

A Case of Immunoglobulin G4-rich Synovitis in a Patient with Ankylosing Spondylitis

서울 학교 의과 학 내과학교실1, 정형외과학교실2, 병리학교실3

구본승1ㆍ윤명재1ㆍ오혜진1ㆍ윤필환2ㆍ김지은3ㆍ신기철1

Immunoglobulin G4-related disease (IgG4-RD) is a novel inflammatory condition characterized by unique pathological features.

IgG4-RD has been found to affect a wide variety of organs including the pancreas, biliary tree, periorbital tissues, salivary glands,

central nervous system, thyroid, lungs, liver, gastrointestinal tract, kidneys, prostate, aorta, retroperitoneum, lymph nodes, breast,

pericardium, and skin. The key morphologic features of IgG4-RD are a dense lymphoplasmacytic infiltrate enriched in

IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis, and occasional eosinophil infiltrate.

We report was a 42-year-old man who had inflammatory back pain and right hip pain during for 1 year. Imaging studies revealed

grade 3 sacroiliitis bilaterally consistent with spondyloarthritis yet also enlargement of lymph nodes at the right external iliac

artery chain. Arthroscopic biopsy of the right hip synovium showed IgG4-rich plasma cells infiltrated in the synovium. This

report describes the first case of IgG4-rich synovitis along with lymphadenopathy in ankylosing spondylitis.


S258

강직성 척추염과 베체트병이 동반된 환자에서 Etanercept에 의해 성공 으로 치료된 1

조선 학교 의과 학 내과학교실 류마티스내과

임균섭ㆍ김진우ㆍ김성 ㆍ소 해ㆍ김동 ㆍ김형호ㆍ김 숙ㆍ김윤성

Behcet’s disease (BD) is characterized with oral or orogenital ulcers and various systemic (eye, skin, joint, central nervous

system, and blood vessels) symptoms. Ankylosing spondylitis (AS), a prototype of seronegative spondiloarthropathy (SNSpA)

group, is a chronic inflammatory disease of the axial skeleton primarily involving the sacroiliac joint and vertebrae. The coex-

istence of BD and AS has been rarely reported. Whether BD is one of SSpA group and Whether BD progresses with sacroiliitis

development have been subjects of debate. We report a patient with concomitant AS and BD successfully treated with etanercept.

In the literature, there are several case reports supporting the effectiveness of NSAIDs, gold preparations, oral, topical or systemic

corticosteroids, colchine and cyclophosphamide in patients with coexisting AS and BD. However, we did not encounter any report

regarding the use of anti TNF-α agent for treatment of these patients except a case of adalimumab. To our knowledge, this

is the first case of a patient with concomittent AS and BD treated with etanercept.


S259

신성 경화증 환자에서 발생한 동기능부 증후군 1

조선 학교 의과 학 내과학교실 류마티스내과

김동 ㆍ김성 ㆍ소 해ㆍ김형호ㆍ김 숙ㆍ김윤성

Systemic sclerosis (SSc) is characterized by the presence of microvascular disease and various patterns of cutaneous and paren-

chymal fibrosis. Manifestations of SSc may occur in numerous tissues and organs, and can be particularly problematic when

present in the lungs, kidneys or heart. Cardiac manifestations are common in SSc, with an estimated clinical prevalence of 15∼

35%. Cardiac involvement includes pericarditis, myocardial disease, conduction abnormalities, and arrhythmia. Sick sinus syn-

drome is described as a combination of symptoms (dizziness, confusion, fatigue, syncope and congestive heart failure) caused

by sinus node dysfunction and manifested by marked sinus bradycardia, sinoatrial block, or sinus arrest. Sinus node dysfunction

is most often found in the elderly, but also rarely in systemic amyloidosis, ischemic heart disease and connective tissue disease.

Sick sinus syndrome is rarely found in patients with SSc. There has been only one case report of sick sinus syndrome in patients

with SSc in review of the literature. Therefore, we report a case of sick sinus syndrome in a 71-year-old female with SSc.


S260

헤노흐-쉔라인 자반증과 동반된 거 세포바이러스 장염 1

경북 학교 의과 학 내과학교실

은정수ㆍ권상훈ㆍ김나리ㆍ임철 ㆍ남언정ㆍ강 모

서론: 헤노흐-쉔라인 자반증(Henoch-Schonlein purpura, HSP)은 장을 침범할 수 있는 소 염으로서 장 막 미란

궤양을 동반하여 2차 감염의 험성을 갖고 있다. 하지만 면역 하자에게 흔히 발생하는 거 세포바이러스

(Cytomegalovirus, CMV)에 의한 감염 장염이 동반되는 경우는 매우 드물다. 본 증례는 HSP의 장 계 침범이 발생

한 환자에서 발병 기부터 CMV에 의한 장염이 발생한 1례를 보고하는 바이다.

증례 : 72세 남자 환자가 3일간의 복통, 변을 동반한 설사 양측 하지에 지되는 피부 자반으로 입원하 다. 내시경

에서 하부식도부터 십이지장까지 다발성 궤양 상부구불창자내시경에서 발 된 막 찰되었고, 복부 CT에서 직장부

터 막창자까지 반 인 장벽 부종이 확인되었다. 소변검사에서 미경 뇨 하루 2,056 mg의 단백뇨가 찰되었다.

피부 생검에서 백 구 괴 염이 있었고 콩팥 생검에서 메산지움의 증식과 IgA C3 침착이 확인되어 HSP로 진단하

으며 고용량 스테로이드를 투여하 다. 치료 후 7일 째 시행한 복부 CT에서 창자의 장벽 부종이 호 되지 않아

감염성 장염 가능성을 확인하기 해 추 내시경을 시행하 다. 내시경상 식도부터 십이지장의 다발성 궤양은 호 되

었으나 장내시경에는 장 막에 다수의 궤양이 지속되었고 복부 CT에도 장벽의 심한 부종이 있었다. 장생검에 CMV

입체가 찰되었고 CMV 면역화학 염색과 CMV 합효소연쇄반응 모두 양성 반응을 보 으며 청 검사에서 CMV

기 항원 양성 추 찰한 CMV IgG 역가 증가 소견 확인되었다. CMV 장염으로 진단하고 항바이러스제로 치료하

다. 이후 증상의 호 추 내시경, 복부 CT에서 호 되었다.


S261

Enterocolic Phlebitis: One Cause of Localized Vasculitis of the Gastrointestinal Tract

Department of Internal Medicine, Division of Rheumatology1, Department of Pathology2, Gachon University Gil Medical Center, Korea

MR Seo1, TE Kim

2, HJ Ryu

1, HJ Baek

1, HJ Choi

1

Vasculitis involving the gastrointestinal tract (GI) often occurs as part of a systemic inflammatory process and is a well-recog-

nized manifestation of small and medium sized vessel vasculitides. Vasculitis of the GI tract may occur in isolation, although

that could progress to a systemic illness. Almost vasculitides in the GI tract involve in arterioles, venules and capillaries, only

affect venules are very rare. Enterocolic phlebitis is a rare disease which affects typically small and medium-sized intramural

and mesenteric veins of the intestines. We report a case of enterocolic phlebitis of the colon. A 38-year-old women presented

hematochezia and severe abdominal pain on the day of admission. She had no history of intestinal disease or systemic disease.

Computed tomography showed extreme thickened wall of the colon and several air bubbles in the colon with diffuse subcutaneous

emphysema in the abdominal wall. An emergency exploration laparotomy and extended right hemicolectomy was performed.

The patient recovered completely after the operation and has been well without other therapy.


S262

A Case of Multicentric Reticulohistiocytosis Responsive to Leflunomide

Department of Rheumatology, Hanyang University Hospital for Rheumatic Disease1, Department of Pathology, Hanyang University College of Medicine2, Korea

Young Bin Joo1, Ki-seok Jang2, Dae-Hyun Yoo1

Multicentric reticulohistiocytosis (MRH) is a rare non-Langerhans cell histiocytic disorder of unknown origin, characterized by

symmetrical arthralgia, erosive or mutilating arthritis, and multiple cutaneous papule on nail bed and any site. Untill now, there

is no international treatment regimen showing effective response. Here, we present a rare case of MRH improved the arthritis

and cutaneous papule after treated with leflunomide. A 39-year-woman complained symmetrical polyarthralgia on shoulder, knee,

elbow, hand in Febrary 2008. On examination, synovitis and a multiple papules along the periungal area and her ears were

observed. Bony erosion on both DIP and PIP were observed on simple radiography. RF was negative and ESR and CRP were

within normal limit. Punched biopsies were taken from the cutaneous papules of the left thumb. All samples from cutaneous

biopsy showed a diffuse multinucleated histoicytic gaint-cell infiltration throughout the dermis, which are positive for vimentin,

CD45, and CD68. She was diagnosed as MRH and then, she was initially treatment with methotrexate 12.5 mg once weekly,

hydroxychloroquine 300 mg and sufasalazine 1g daily for 15 months. There was a slight improvement of arthralgia in the early

course but eventually, arthralgia and nodules were increased. April, 2011, synovial biopsy from knee joint was done, and also

showed a diffuse infiltration of multinucleate giant cells and glassy histiocytes. Then, Leflunomide 10 mg daily, prednisolone

30mg (it was tapered to 2.5 mg through 18 months) and bisphosphonate were tried. Arthralgia was markedly improved 6 month

later. Recently, after 24 months followed up, no symptom excepted left wrist arthralgia was observed. Also numerous cutaneous

papules on the periungal area and pinnae of her ears were dramatically disappeared. However, it is not certain that this clinical

response is due to only leflunomide or other combined drugs such as prednisolone or bisphosphonate. More long term followup

and case reports may be helpful to come to conclusion.


S263

난치성 성인형 스틸병 환자에서 Abatacept로 치료를 시도한 환자 5


윤명재ㆍ오혜진ㆍ구본승ㆍ주상 ㆍ김경록ㆍ이은

서론: 성인형 스틸병은 드문 신 염증성 질환이며, 발열, 염, 피부발진과 백 구 증가증을 특징으로 한다. 부분의

환자는 스테로이드와 MTX를 포함한 DMARDs에 좋은 치료 반응을 보인다. 그러나 일부 난치성 환자의 경우에는 TNFa

inhibitor를 포함함 생물학 제제의 사용에도 불구하고 치료반응을 보이지 않는다. 우리는 난치성 성인형 스틸병 환자에서

Abatacept를 사용하여 치료를 시도한 5례를 보고한다.

방법: 환자들은 Abatacept를 사용하기 에 평균 5년 7개월의 유병기간을 가진 만성 인 환자들이며, steroid MTX를

포함한 DMARDs, TNF-a inhibitor 치료를 받았으나 효과가 없었다. 5명 2명에서는 Tocilizumab 치료가 시행되었고, 1명

은 rituximab을 사용하 으나 역시 효과 부족으로 단하 다. Abatacept는 500 mg를 첫 2번은 2주 간격으로, 이후에는

4주 간격으로 투여하 으며, 치료하는 동안 일정한 주기로 임상 소견평가 액검사가 시행되었다.

결과: 5명의 환자들 4명은 다발성 염이 주증상 이었으며, 1명은 발열 근육통이 주증상이었다. 염이 주증상

인 4명 1명은 Abatacept 투여 6개월 이후 종창 압통 의 수가 각각 17개→6개, 9개→0개로 히 감소하 으며,

다른 1명은 각각 3개→1개, 3개→1개로 감소하 다. 이외에 2명은 종창 과 압통 의 수에 큰 변화는 없었으나,

반 인 증상의 완화를 보 다. 발열 근육통 등의 신 증상이 주증상이었던 1명에서도 Abatacept 투여 후에 증상의

호 을 보 다. 5명의 환자들 ESR과 CRP 등의 염증 수치는 2명에서는 변화가 거의 없었으나, 3명은 감소하는 경향을

보 다. Abatacept 투여 추 찰 기간 (7∼13개월) 동안 감염증의 발병을 포함한 부작용은 찰되지 않았다.

결론: 기존의 DMARDs 치료 TNFa inhibitor 등의 치료에 반응하지 않는 난치성 성인형 스틸병 환자에서 Abatacept

가 치료의 안이 될 수 있으리라 기 한다.


S264

A Case of Primary Biliary Cirrhosis in Overlap Syndrome of Systemic Sclerosis and Rheumatoid Arthritis

Division of Rheumatology, Department of Internal Medicine, Gachon University Gil Hospital, Korea

Kyoung Hwa Lee, Mi Ryoung Seo, Han Joo Baek, Hyo Jin Choi

Primary biliary cirrhosis (PBC) is an autoimmune liver disease occasionally combined in patients with rheumatic diseases such

as systemic sclerosis, Sjogren’s syndrome. But there are a few reports about the primary biliary cirrhosis that occurred in patient

with overlap syndrome of systemic sclerosis and rheumatoid arthritis. A 36 year-old female was diagnosed as diffuse systemic

sclerosis because of skin thickening on face, both forearm and fingers with pitting scar, interstitial lung disease on chest CT

with restrictive pulmonary function test and positivity of anti-Scl-70 antibody in Apr 2007. Rheumatoid arthritis was diagnosed

in Oct 2010 due to persistent hand arthritis, positivity of anti CCP antibody and rheumatoid factor, and both carpal bone erosions

on hand x-ray. Her arthritis was controlled after adalimumab treatment. In Jan 2012, we decided to stop adalimumab because

of her pregnancy. In Oct 2012, one month after delivery, she complained of a hand arthritis and fatigue. Laboratory exam showed

ESR 53 mm/hr, CRP 1.34 mg/dL, AST 223U/L, ALT 265U/L, alkaline phosphatase 929U/L, gamma-GT 703U/L and positive

anti-mitochondria antibody. Histology of liver biopsy revealed moderate porto-periportal and mild lobular inflammation with bile

duct inflammation consistent with primary biliary cirrhosis. She was treated with prednisolone 15mg/day and hepatonics. Her

arthritis and transaminase levels have been improving gradually till now.


S265

A Case of Behçet's Disease with Esophagopharyngeal Ulcers


Jin-Won Jang, Yun-Jung Choi, Ha-Yong Yoon, Won Seok Lee, Wan-Hee Yoo

Behçet's disease (BD) is a heterogeneous disorder with variable involvement of many organ systems, mainly including, mucocuta-

neous, articular, vascular, ophthalmological and gastrointestinal systems. Gastrointestinal BD have been reported to be rare but

are difficult to treat and mainly affects the terminal ileum, cecum, and ascending colon, although esophageal and pharyngeal

lesions are rarely seen. A 64-year-old male had suffered from recurrent oral and genital ulcers for 20 years and complained

pharyngeal and substernal discomfort for 3 months. There were multiple oral ulcers on tongue and lip with multiple folliculitis-like

skin lesions on face, scalp and trunk. Gastroesophageal fiberscopy revealed multiple, deep ulcers with distinct border and irregular

base on pharynx and upper esophagus (Fig. 1, 2) without specific lesion on stomach except atrophic gastritis. A diagnosis of

BD was made with characteristic clinical symptoms, including recurrent oral, genital ulcers, folliculitis and positive Pathergy

test. He had no history of recent infections (virus, bacteria and Candida albicans), radiation, ingestion of corrosive substances,

certain pills, and Crohn's disease. Thus he has been treating with prednisolone, colchicines, dapsone and sulfasalazine. We here

present an unusual case of Behçet's disease associated with esophageal and pharyngeal ulcers, and BD should be considered

in the differential diagnosis of esophagopharyngeal ulcers.


S266

흉선종과 동반하여 나타난 자가면역 병증 1

순천향 학교 서울병원 내과학교실

정신옥ㆍ김 숙

서론: 흉선종과 련된 자가면역병증은 매우 다양하며 이 증 근무력증이 가장 흔하게 동반되나 쇼그 병이나 면역

결핍증은 드물다. Good’s syndrome은 성인 발생 면역 결핍증으로 매우 드물며 서구에서는 흉선종 환자의 5∼10%, 일본에

서는 0.2∼0.3%에서 나타난다 형 인 Good’s syndrome에서는 감마 로블린 증, B-세포 결핍이 찰된다 감염 방

은 Good’s syndrome의 후를 향상시키며 정기 IVIG 투여가 필요하다 본 증례 환자에서도 MDS, 쇼그 병과 Good’s

syndrome 동반 진단 하에 감염의 빈도를 낮추기 한 IVIG 투여 후 경과 찰 이다.

증례: 76세 여자 환자로 심한 건조안과 입마름을 주소로 진료 의뢰되었다. 환자는 2007년, 2008년 결핵성 뇌막염 진단.

2009년 침윤성흉선종(invasive thymoma), pure red cell aplasia 진단하고 흉선 제술 시행, thymomectomy 시행, 2010년 MDS

동반 진단과 결핵성 뇌막염이 재발 되었다. 2011년 both thigh weakness 지속되었으나 근 도, 신경 도검사, 뇌 자기공명

검사에서 특이 소견 없고 작년부터 거동이 어려워 재활치료 유지하던 잦은 상기도 감염이 반복되며 고열로 최근 입원

치료 이 다.

진찰 검사실 소견: 양측 시야 흐림 소견과 양쪽 상하지 약감 동반되었다. 말 액검사에서 백 구 1,400/mm3 (호 구

29.8%, 림 구 56.7%, 호산구 1.6%), 색소 8.8 g/dL, 소 236,000/mm3이었고, 구 침강속도 59 mm/hr, C-반응단백

0.71 mg/dL 다. 청 생화학 검사에서 BUN/creatinine 5/0.39 mg/dL, 알부민 2.8 g/dL, Ca 7.9 mg/dL, AST/ALT 17/9 IU/L,

총 빌리루빈 0.3 mg/dL, LDH 235 IU/L. 자가항체 검사에서 ANA양성(1：320), Anti-ds-DNA 3.75IU/mL, C3/C4 87/32 mg/dL

Immunoglobulin G 1096 mg/dL Immunoglobulin A 186 mg/dL, Immunoglobulin M 28 mg/dL, Anti SSa/Ro Ab 양성, Anti SSb/La

Ab 음성, Anti RNP Ab 음성, Anti Scl 70 Ab 음성, Anti Centromere Ab 음성 나타났다.

경과: 동반된 폐렴은 항생제 치료로 호 되었고 심한 구강 건조, 안건조, ANA와 Anti SSa/Ro Ab 양성으로 쇼그 병과

면역 로불린 하와 반복되는 감염으로 Good’s syndrome 진단, 한 이 의 병력상 MDS 동반 진단을 고려할 때 흉선종

과 련된 자가면역병증이 합당했다. 재활치료 유지 후에 고령인 과 추 후 감염증의 빈도를 낮추기 해 IVIG 치료(20

g/일, 5일간)를 시행 하 다.


S267

Dysphagia Caused by Ossification of the Cervical Anterior Longitudinal Ligament

순천향 학교 서울병원 내과학교실

곽윤미ㆍ김 숙

Degeneative changes in the cervical spine can produce osteophytes and other hypertrophic abnormalities including ossification

of the anterior longitudinal ligament (OALL). Cervical osteophytes including OALL are common whereas asymptomatic in the

aging population. Dysphagia resulted from cervical OALL, although uncommon, is an important and treatable cause of dysphagia

that must be identified. A 57-years-old male patient presented with a 5-month history of dysphagia, which had progressed for

3 months. He also had pain and motion limitation of neck. Neurological examination showed difficulty in swallowing solid food.

Simple lateral radiography and computed tomography scan showed OALL at the level of C3-C5. Magnetic resonance images

(MRI) revealed compression of oropharynx and esophagus caused by OALL. He underwent the removal of OALL by anterior

approach. Careful dissection of OALL was carried out so at not to injure the esophagus. OALL was resected by using a high

speed drill. After surgery, the ossified mass was removed successfully. He recovered from swallowing difficulty on full consistency

diet 2 weeks after surgery.

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