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United States Immunodeficiency Network

(USIDNET)

Annual Face-to-Face Meeting January 9-10, 2017

Bethesda North Marriott Hotel

& Conference Center

Agenda

Participants / DSWG

Enrolling Institutions

Enrollment

Queries

Methods for Patient Recruitment

PI CONNECT

Specific Aims for USIDNET

USIDNET Events 2016

Educational Resources

Projects and Updates

Publications

USIDNET Repository

Support / Grants

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USIDNET ANNUAL FACE-to-FACE MEETING

January 9-10, 2017 Bethesda North Marriott Hotel

5701 Marinelli Rd Rockville, MD 20852

“Resources to Assist Investigations in Primary Immune Deficiency Diseases” Room: White Oak

Emergency Contacts Tara Caulder: 443-824-0076 Marla Goldsmith: 856-287-2524 Julieann Magnusson 410-365-2802

Monday, January 09, 2017

9:00-9:30AM Arrival and Continental Breakfast

9:30-9:35AM Welcome & Introduction of participants (5 min) Charlotte Cunningham-Rundles, MD PhD, USIDNET Principal Investigator

9:35-9:45AM Overview of USIDNET Program / NIH Funding Opportunities for PIDD (10 min) Frosso Voulgaropoulou, PhD, USIDNET Project Scientist

9:45-10:00AM What is USIDNET? Overview and Progress (15 min) Charlotte Cunningham-Rundles, MD PhD, USIDNET Principal Investigator

10:00-10:45AM Registry Overview, Updates, and Future Upgrades: A deeper dive into the numbers; Where USIDNET Registry is headed with REDCap and Why (30 min)

Marla Goldsmith, USIDNET Registry Manager Tara Caulder, USIDNET Project Director

Discussion (15 min)

10:45-11:00AM Coffee Break (15 min)

11:00-12:00PM Use of USIDNET Data in Publications (60 min) Moderator: Kathleen Sullivan, MD, PhD, USIDNET Co-Investigator Round Table Discussion: How Can USIDNET Help Fellows and FIT Programs? Round Table Discussion: Turning Abstracts into Manuscripts

12:00-12:45PM New and Continuing Initiatives (Part 1): APS Type 1 & ADA SCID (45 min) Moderator: Luigi Notarangelo, MD, USIDNET Co-Investigator

New Initiative: APS 1

Discussion: What is APS-1 and how can USIDNET help? (15 min) o Mikhail Lionakis, MD, PhD, Chief, Fungal Pathogenesis Unit, NIAID/NIH

Discussion: APS-1 Patient and Community perspectives (15 min) o Jennifer Orange, Board of Directors, APS Type 1 Foundation

Continuing Initiative: ADA SCID

Discussion: ADA SCID in the USIDNET Registry (15 min) o Donald Kohn, MD, Department of Pediatrics and MMP, UCLA

12:45-1:15PM New Initiatives (Part 2): New Defects and New Directions (30 min) New Defects: PIK3CD, NFKB, STAT 3

o Luigi Notarangelo, MD, USIDNET Co-Investigator

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12:45-1:15PM New Initiatives (Part 2): New Defects and New Directions (cont.) New Directions: IUIS Project, NICHD RFA

o Kathleen Sullivan, MD, PhD, USIDNET Co-Investigator/PICONNECT Principal Investigator

1:15-2:00PM Working Lunch (45 min) with Discussion of Initiatives Moderator: Luigi Notarangelo, MD, USIDNET Co-Investigator Discussion: Expanding the role of the Disease Specific Working Groups

2:00-2:05 PM Immune Deficiency Foundation (IDF) Research Grant (5 min) Marcia Boyle, Immune Deficiency Foundation, President and Founder

2:05-2:30PM Following Infants with Low Lymphocytes: FILL project goals & progress (25 min) Jennifer Puck, MD, USIDNET Co-Investigator Luigi Notarangelo, MD, USIDNET Co-Investigator

2:30-3:00PM USIDNET Contributors: Making the Best Registry (15 min) Moderators: Kate Sullivan MD PhD, and Charlotte Cunningham-Rundles MD PhD Collaborators: Buffy Garabedian, Connor Wakefield, Mary Ruehle

3:00-3:15PM Break (15 min)

3:15-4:00PM Involving Patients in USIDNET: PI CONNECT and PROMIS 29 QOL (45 min) Kathleen Sullivan, MD, PhD, USIDNET Co-Investigator & PI CONNECT Principal Investigator Christopher Scalchunes, IDF Vice President of Research & PI CONNECT Co-investigator Julieann Magnusson, IDF Research Coordinator

Discussion: How to Involve Patients Locally

Kathy Owl Green, John Boyle, Elizabeth Secord, Rebecca Marsh, Karin Chen, Morna Dorsey, Jennifer Leiding

Discussion: Use of Social media

FIT chairs and other experts!

4:00-5:00PM Working with Industry: Another Model (60 min) Moderator: Ramsay Fuleihan, MD, USIDNET Co-Investigator

Shire Awardees:

Sarah Barmettler, MD

Avni Joshi, MD

Edith Schussler, MD, PhD

5:00-5:30PM Industry as Our Partner and New Initiatives (30 min) Moderator: Charlotte Cunningham-Rundles, MD, PhD, USIDNET Principal Investigator

Discussion: What Works? What’s next?

Industry Partners: Chris Rabbat (Shire); Deborah Galinas and Carol Dagney (Grifols); Ann Bulinger (CSL Behring); Michelle Park (ADMA Biologics); Kristine David, Nadia Salem, and Joseph Wiley (Sigma Tau)

5:30-5:45PM Education: Summer School, Visiting professors and Scholars, and More (15 min) Charlotte Cunningham-Rundles, MD PhD, USIDNET Principal Investigator

Kathleen Sullivan, MD, PhD, USIDNET Co-Investigator & PICONNECT Principal Investigator

5:45-6:00PM Repository (15 min) Jennifer Puck, MD, USIDNET Co-Investigator

6:00 – Dinner: Discussion USIDNET Physician Survey: What do you want to see from us? How do you want to see it?

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USIDNET Face to Face Meeting - January 9 - 10, 2017

USIDNET Steering Committee Members

Charlotte Cunningham-Rundles, MD, PhD – Principal Investigator Mount Sinai Medical Center, New York, NY

Luigi Notarangelo, MD – Co-Principal Investigator Children’s Hospital of Boston-Harvard, Boston, MA

Jennifer M. Puck, MD – Co-Principal Investigator University of California, San Francisco, CA

Kathleen Sullivan, MD, PhD – Co-Principal Investigator Children’s Hospital of Philadelphia, Philadelphia, PA

Ramsay Fuleihan, MD – Co-Principal Investigator Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL

Frosso Voulgaropoulou, Ph.D. – Project Scientist National Institute of Allergy and Infectious Diseases, Rockville, MD

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USIDNET / IDF Administrative Support

Marcia Boyle – President and Founder

Immune Deficiency Foundation (IDF)

Towson, MD

Sarah Rose - IDF Chief Financial Officer


Towson, MD

Christopher Scalchunes - IDF Vice President of Research


Towson, MD

Tara Caulder - USIDNET Project Director


Towson, MD

Marla Goldsmith – USIDNET Registry Manager


Towson, MD

Julieann Magnusson – Research Coordinator


Towson, MD

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INVITED GUESTS

Becky Buelow, MD｜Medical College of Wisconsin｜FIT AAAAI, current

Bob Honigberg, MD, MBA｜Shire

Buffy Garabedian, RN, MSLS｜NIH-NHGRI｜USIDNET Enrolling Centers

Carol Dagney, MSL｜Grifols

Connor Wakefield ｜Cincinnati Children's Hospital Medical Center｜USIDNET Enrolling Centers

Dan Rotrosen, MD｜National Institutes of Health (NIH)｜NIH

Deborah Gelinas, MD｜Grifols

Donald Kohn, MD｜University of California, Los Angeles｜ADA SCID

Edith Schussler, MD｜Icahn School of Medicine at Mount Sinai｜Baxalta Awardee

Elizabeth Secord, MD｜Children's Hospital of Michigan｜USIDNET Enrolling Centers

Jennifer Leiding, MD｜University of South Florida｜STAT-3

Jennifer Orange ｜APS-1 Foundation｜APS-1 Foundation

Jim McNamara, MD｜National Institutes of Health (NIH)｜NIH

John Boyle｜Immune Deficiency Foundation｜Patient/Caregiver Representative

Joseph Wiley, MD｜Sigma Tau Pharmaceuticals

Karin Chen, MD｜University of Utah｜NFKB

Kathy Owl Green, RN, MBA, BSN, CPN｜Patient / Caregiver Representative

Kristine David, RD｜Sigma Tau Pharmaceuticals

Ladonna Murphy, PharmD｜CSL-Behring

Linda Griffith, MD, MHS, PhD｜National Institute of Allergy & Infectious Diseases (NIAID)｜NIH/PIDTC

Mary Ruehle, MS, RN, CPN, APHN-BC｜Children's Hospital of Michigan｜USIDNET Enrolling Centers

Michail Lionakis, MD, ScD｜National Institute of Allergy & Infectious Diseases (NIAID), NIH｜APS-1

Michelle Park, PharmD｜ADMA Biologics

Morna Dorsey, MD, MMSC｜University of California, San Francisco｜AAAAI PID committee

Nadia Salem, PharmD｜Sigma Tau Pharmaceuticals

Rebecca Marsh, MD｜Cincinnati Children's Hospital Medical Center｜USIDNET Enrolling Centers

Sara Barmettler, MD｜Harvard Medical School - Massachusetts General Hospital｜Baxalta Awardee

Sarah Spriet, DO｜Walter Reed Allergy and Immunology｜FIT ACAAI, current

Shan Chandrakasan, MD｜Cincinnati Children's Hospital Medical Center｜CIS - ECI co-chair

Tammy Peng, MD｜University of California, Los Angeles｜FIT ACAAI, upcoming

Thomas Esch, PhD｜National Institutes of Health (NIH)｜NIH

Vanessa Bundy, MD｜University of California, Los Angeles｜FIT AAAAI, upcoming

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Disease Specific Working Group Members – 2016

SCID/CID: Jennifer Puck - Chair John Routes, Luigi Notarangelo, Morna Dorsey, Mort J. Cowan, Robert Nelson

XLA: Vivian Hernandez-Trujillo - Chair Artemio Jongco, Francisco Bonilla, Hans D. Ochs, Hillary Hernandez-Trujillo, Leman Yel

HIGM: Ramsay Fuleihan – Chair Leman Yel, Maite de la Morena, Manish Ramesh, Niraj C. Patel, Troy Torgerson

WAS: Hans D. Ochs, Jordan Scott Orange , Sumathi Iyengar, Luigi Notarangelo

CVID: Charlotte Cunningham-Rundles – Chair Adina Kay Knight, Francisco Bonilla, Jennifer Heimall, John Routes, Mark Ballow, Shradha Agarwal, Warren Strober, Zuhair Ballas

COMPLEMENT: Elie Haddad

NEMO: Jordan Orange – Chair Laurence Cheng; Eric Hanson

DGS: Kate Sullivan – Chair Elena Perez, Ivan Chinn, Javeed Akhter, Lisa Kobrynski, Vivian Hernandez-Trujilo

CGD / LAD: Artemio Jongco, Christa Zerbe, Imelda Celine Hanson, Jennifer Leiding, Joyce Yu, Lisa Kobrynski, William Muller

IPEX / ALPS / APECED: Troy Torgerson – Chair; Tom Fleischer – Co-Chair Jack Bleesing, Joao Bosco Oliveira, Morna Dorsey

Hyper IgE: Alexandra Freeman – Chair Jennifer Heimall, Jennifer Puck, Niraj Patel, Troy Torgerson

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USIDNET Enrolling Institutions

There are currently 45 USIDNET enrolling institutions, which consist of 42 academic medical institutions and 3 private practices (covered under SAIRB.) 4 new site were added in 2016.

Site Location Principal Investigator Co-Investigator

Advocate Hope Children’s Hospital Oak Lawn, IL Dr. Javeed Akhter

Allergy Associate of the Palm Beaches N Palm Beach, FL Dr. Mark Stein

Altru Health System (New) Grand Forks, ND Dr. Fatima Khan

Children’s Hospital of Boston Boston, MA Dr. Francisco Bonilla Dr. Raif Geha

Children’s Hospital of Los Angeles Los Angeles, CA Dr. Jonathan Tam

Children’s Hospital Orange County Orange, CA Dr. David Buchbinder

Children's Hospital Minnesota St. Paul, MN Dr. Tamara Pozos Sara Green, RN

Children's National Washington DC Dr. Burcin Uyungil

CHU Sainte-Justine Montreal, Canada Dr. Elie Haddad

Cincinnati Children’s Hospital Medical

Center

Cincinnati, OH Dr. Rebecca Marsh

Children’s Hospital of Pennsylvania Philadelphia, PA Dr. Kate Sullivan Dr. Kim Nichols Dr. Soma Jyonouchi Dr. Jen Heimall

Cleveland Clinic Cleveland, OH Dr. James Fernandez

Daniel Suez Allergy, Asthma, &

Immunology

Irving, TX Dr. Daniel Suez

Duke University Medical Center Durham, NC Dr. Rebecca Buckley Dr. Patricia Lugar

Emory University Atlanta, GA Dr. Lisa Kobrynski

Hackensack University Medical Center Hackensack, NJ Dr. Kathleen Haines

Joe DiMaggio Children’s Hospital Hollywood, FL

Johns Hopkins Hospital Baltimore, MD Dr. Beth M. Younger

Levine Children’s Hospital Charlotte, NC Dr. Niraj Patel

Louisiana State University Baton Rouge, LA Dr. Ricardo Sorenson Dr. Ken Paris

Massachusetts General Hospital Boston, MA Dr. Jolan Walter Dr. Jocelyn Farmer

Mayo Clinic Rochester, MN Dr. Avni Joshi

Medical College of Wisconsin Milwaukee, WI Dr. John Routes Dr. James Verbsky

Miami Children’s Hospital Miami, FL Dr. Vivian Hernandez-Trujillo

Mt. Sinai School of Medicine New York, NY Dr. Charlotte Cunningham-

Rundles

Dr. Shradha Agarwal

NIAID Washington DC Dr. Warren Strober

NIH – NHGRI Bethesda, MD Elizabeth Garabedian RN,

MSLS

Rainbow Babies and Children’s Hospital Cleveland, OH Dr. Leigh Kerns

Robert H. Lurie Children’s Hospital of

Chicago

Chicago, IL Dr. Ramsay Fuleihan Dr. William Muller Dr. Nashmia Qamar

Stonybrook Children’s Stony Brook, NY Dr. Susan Schuval

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Site Location Principal Investigator Co-Investigator

Texas Children’s Hospital Houston, TX Dr. Celine Hanson

Dr. Jordan Orange

United States Immunodeficiency

Network

Towson, MD Dr. Ramsay Fuleihan

University of California, San Francisco San Francisco, CA Dr. Jennifer Puck Dr. Laurence Cheng

Dr. Diane Wara

Dr. Mort Cowan

Dr. Kathleen Gunding

University of Colorado, Denver Denver, CO Dr. Charles Kirkpatrick

University of Iowa Iowa City, IA Dr. Zuhair Ballas Dr. Mary Beth Fasano

University of Michigan (New) Ann Arbor, MI Dr. Kelly Walkovich

University of Missouri (New) Kansas City, MS Dr. Nikita Raje

University of South Florida Tampa, FL Dr. Jennifer Leiding

University Texas Southwestern Medical

Center

Dallas, TX Dr. Maite de la Morena

University of Utah Salt Lake City, UT Dr. Karin Chen

University of Wisconsin Madison, WI Dr. Christine Seroogy Dr. James Gern

Wayne State University Detroit, MI Dr. Elizabeth Secord

Women and Children’s Hospital of

Buffalo

Buffalo, NY Dr. Heather Lehman

Washington University Saint Louis, MO Dr. Megan Cooper

Working with Physician to Establish Protocol

Indiana University-Purdue University Indianapolis Dr. Robert Nelson

Arkansas Children’s Hospital Dr. Amy Scurlock

Children’s Hospital of Pittsburgh Dr. Hey Chong

Drexel University Dr. Daniel Conway

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USIDNET Registry Site Enrollment 2016

As of January 1, 2017, the total USIDNET Registry enrollment from all sources is 6,162

Site Enrolled Site Enrolled

Advocate Hope Children's Hospital 85 Medical College of Georgia 6

Alabama Allergy and Asthma Center 3 Medical College of Ohio 1

Allergy Assoc. of the Palm Beaches 9 Medical College of Wisconsin 90

Allergy Asthma & Clinical 1 Memorial Healthcare Systems 64

Allergy, Asthma & Imm. Associates 1 Miami Children's Hospital 15

Allergy, Asthma & Sinus Center 1 Midland Allergy Clinic 1

Altru Health System 6 Midwest Immunology Clinic 71

Ann and Robert H. Lurie Childrens Hospital 38 Mt. Sinai 247

Baylor College of Medicine 1 National Jewish Center 4

Center for Allergy, Asthma & Immunology 2 Nationwide Children's Hospital 1

Center for Blood Research 2 NIH - NHGRI 398

CentraCare Women & Children 1 Northshore Allergy & Immunology 1

Children's Hospital Central California 1 Olmsted Medical Group 1

Childrens Hospital of LA 3 Oncology Hematology Associates 1

Childrens Hospital of Michigan 96 Oregon Health Sciences U. 3

Children's Hospital of Orange County 6 Presbyterian Med. Center 1

Children's Hospital, Boston 99 Robert Wood Johnson Med School 6

Children's Hospitals and Clinics of MN 1 Seattle Children's Hospital 55

Children's National Medical Center 65 St. Louis Childrens Hospital 1

CHOP Immunology 495 Stony Brook Children's Hospital 1

CHU Sainte-Justine 48 Texas Childrens Hospital 3

Cincinnati Children's Hospital Medical Center 96 UCLA Medical Center--LA 1

Cleveland Clinic Foundation 18 Univ. of CO Health Science Ctr 1

Clinical Research Center, NIH 18 Univ. of Iowa Hospital 41

Coast Allergy Asthma Center 1 Univ. of Mich Health System 5

Columbia-Presbyterian Med Center 1 Univ. of Nebraska Med Ctr 1

Connecticut Children's Medical Center 7 Univ. of Texas--SW Medical Center 1

Daniel Suez MD AAIC PA 107 University Hospital & Clinic 7

Duke Medical Center 154 University Hospitals of Cleveland 1

Emory Children's Center 3 University of Alabama 1

Hackensack UMC 7 University of California San Francisco (UCSF) 196

Harrisonburg Medical Associates 1 University of Maryland 2

Howard Hughes Med. Institute 3 University of Utah 46

Howard University Hospital 1 University of Wisconsin-Madison 2

IDF 1337 University Suburban Health Center 2

Institute for Asthma & Allergy 1 USIDNET 1909

Johns Hopkins Childrens Center 1 Vanderbilt ASAD 1

Levine Children's Hospital 58 Vanderbilt Univ. Med Center 2

Littlestown Family Medicine 1 Wake Forest University 2

Logan Regional Hospital 1 Washington University 36

Lucile Packard Children's Hospital 1 Women and Childrens Hospital of Buffalo 14

Massachusetts General Hospital 24 Yale U. School of Med. 3

Mayo Clinic 111 Yale University 1

Total 6162

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USIDNET Enrollment Sources 2016

In 2016, the USIDNET Registry had 1051 patients registered & initial visits entered via various sources listed below.

USIDNET Enrolling Sites

Site Enrolled

Advocate Hope Children's Hospital 9

Altru Health System 6

Childrens Hospital of Michigan 29

Children's Hospital of Orange County 2

Children's Hospitals and Clinics of MN 1

Children's National 24

CHOP Immunology 27

Cincinnati Children's Hospital Medical Center 96

Connecticut Children's Medical Center 4

Daniel Suez MD AAIC PA 5

Duke Medical Center 6

Hackensack UMC 3

Massachusetts General Hospital 24

Mayo Clinic 75

Medical College of Wisconsin 37

Memorial Healthcare Systems 1

Mt Sinai 10

NIH - NHGRI 153

Stony Brook Children's Hospital 1

Univ. of Mich Health System 5

University of California San Francisco (UCSF) 20

University of Utah 22

USIDNET 455

Washington University 36

Grand Total 1051

FILL Enrolling Sites

Site FILL FILL Visits &

Registry Visits

Childrens Hospital of Michigan 20 -

CHOP Immunology 1 -

Medical College of Wisconsin 2 1

Mt. Sinai 6 1

University of California San Francisco (UCSF) 8 10

University of Utah 1 -

Grand Total 38 12

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USIDNET Enrollment by Disease Category

As of January 1, 2017, the USIDNET Registry has 6,162 patients enrolled into the following disease categories

Category Total Participants Original Registry

Agammaglobulinemia 431 200

ALPS 12 -

Antibody defect 1925 377

Autoinflammatory disease 7 -

Chronic granulomatous disease 548 384

Class switch defect 153 105

Complement deficiency 26 -

DNA repair 23 -

Dyskeratosis congenita 2 -

HLH 53 -

Hyper-IgE Syndrome 91 -

Immune dysregulation 26 -

Innate immune deficiency 75 -

Mucocutaneous candidiasis 52 -

Neutrophil Disorders (non CGD) 12 -

Other Congenital Defects 1 -

SCID/CID 430 127

Thymic defect 486 56

Unclassified Immune Deficiency 4 -

WAS 242 170

FILL (Infant with Low Lymphocytes) 38

PICONNECT (Awaiting Clinician-Confirmed DX) 1527 -

Total 6162 1419

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USIDNET Enrollment by Diagnosis A full list of diagnoses for all USIDNET participants can be found below.

Diagnosis Patients

Agammaglobulinemia 431

Agammaglobulinemia of unknown cause or unlisted gene defect 18

BTK deficiency, X-linked agammaglobulinemia (XLA) 399

PI3KR1 deficiency (AR)-agammaglobulinemia 14 ALPS 12

ALPS, unknown gene defect 3

ALPS-Caspase 8 1

ALPS-Caspase10 1

ALPS-FAS 7 Antibody Defect 1925 CARD 11 GOF (BENTA) 1

CD19 deficiency 1

Common variable immune deficiency with no gene defect specified (CVID) 1588

Hypogammaglobulinemia of unknown cause or unlisted gene defect 170

IgA Deficiency 51

IgG subclass deficiency 17

IgG subclass deficiency with IgA deficiency 3

Myelodysplasia with hypogammaglobulinemia, unknown gene defect 1

PI3K-d GOF 8

Specific antibody deficiency with normal Ig concentrations and normal numbers of B cells 69

TACI deficiency 5

Transient hypogammaglobulinemia of infancy with normal numbers of B cells 11

Auto-inflammatory Disease 7

Autoinflammatory disease, unknown defect 3

CIAS1 disorders 3

Familial Mediterranean Fever 1

Chronic Granulomatous Disease 548

Abnormal neutrophil killing unknown defect 156

Autosomal recessive CGD – p22 phox deficiency (CYBA) 5

Autosomal recessive CGD – p47 phox deficiency (NCF1) 18

Autosomal recessive CGD – p67 phox deficiency (NCF2) 3

X-linked CGD - gp91 phox deficiency (CYBB) 366

Class Switch Defect 153

AID deficiency 2

CD40 deficiency 1

CD40L deficiency 28

Hyper IgM due to uncertain or unlisted cause 122

Complement Deficiency 26

C1 inhibitor deficiency 5

C2 deficiency 13

C3 deficiency (LOF) 2

C4 deficiency 1

Complement deficiency due to uncertain or unlisted cause 5

DNA Repair 23

Ataxia-telangiectasia 23

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Diagnosis Patients

Dyskeratosis Congenita 2

Dyskeratosis congenita, unknown gene defect 2

HLH 53

Chediak-Higashi syndrome 9

Hemophagocytic syndrome (HLH), unknown defect 13

Perforin deficiency (FHL2) 2

SH2D1A deficiency (XLP1) 5

STXBP2 / Munc18-2 deficiency (FHL5) 8

UNC13D / Munc13-4 deficiency (FHL3) 5

XIAP deficiency (XLP2) 11

Hyper-IgE Syndrome 91

Hyper IgE syndrome AD STAT3 91

Immune Dysregulation 26

CD25 deficiency 1

IL-10 deficiency 1

IPEX, immune dysregulation, polyendocrinopathy, enteropathy X-linked 12

Pleomorphic autoimmune disorder with unknown gene defect 10

STAT3 GOF mutations 2

Innate Immune Deficiency 75

CD16 defect 2

GATA2 deficiency (MonoMac) 38

IFN-g receptor 1 deficiency 7

IL-12 and IL-23 receptor b1 chain deficiency 2

IRAK-4 deficiency 1

NK cell deficiency not specified 1

Predisposition to severe viral infections, unknown gene defect 4

STAT1 deficiency (AD LOF) 1

TLR3 deficiency 1

WHIM (Warts, Hypogammaglobulinemia, infections, Myelokathexis) syndrome 18

Mucocutaneous Candidiasis 52

APECED (APS-1), autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy 45

CARD9 deficiency 2

Mucocutaneous candidiasis, unknown defect 1

STAT1 GOF 4

Neutrophil Disorders (non CGD) 12

Abnormal neutrophil migration, unknown defect 1

Leukocyte adhesion deficiency type 1 (LAD1) 7

Neutropenia, unknown defect 3

Schwachman-Diamond Syndrome 1

Other Congenital Defects 1

Pulmonary alveolar proteinosis 1

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Diagnosis Patients

SCID / CID 430

Adenosine deaminase (ADA) deficiency 62

Cartilage hair hypoplasia (CHH) 10

CD3d deficiency 2

CD45 deficiency 1

Cernunnos/XLF deficiency 1

Combined immune deficiency with unknown or unlisted genetic cause 37

Comel-Netherton Syndrome 4

DCLRE1C (Artemis) deficiency 5

DOCK8 deficiency (Hyper-IgE) 19

Ectodermal dysplasia with immunodeficiency due to unknown genetic cause 3

EDA-ID IKBA GOF mutation (ectodermal dysplasia, immune deficiency 3

EDA-ID, NEMO /IKBKG deficiency (ectodermal dysplasia, immune deficiency) 20

gc deficiency (common gamma chain SCID, CD132 deficiency) 49

IKBKB deficiency 1

IL7Ra deficiency 11

Immune deficiency with syndromic features and unknown gene defect 1

JAK3 deficiency 6

Ligase IV deficiency 3

LRBA deficiency 2

MAGT1 deficiency (XMEN) 2

MHC class II deficiency group C (Bare lymphocyte syndrome type II 2

Omenn syndrome, unknown gene defect 7

Purine nucleoside phosphorylase (PNP) deficiency 1

RAG 1 deficiency 11

RAG 2 deficiency 5

Reticular dysgenesis 3

Schimke Immunoosseous Dysplasia 1

SCID, unknown gene defect 156

TCRα deficiency 1

ZAP-70 deficiency 1

Thymic Defect 486

CHARGE syndrome, unknown gene defect 3

DiGeorge/velocardiofacial syndrome, unknown defect 483

Unclassified Immune Deficiency 1531

Immunodeficiency Unknown Cause 4

Awaiting Clinician-Confirmed Diagnosis 1527

FILL Program 38

Infant with Low Lymphocytes awaiting further evaluation 38

Wiskott-Aldrich Syndrome 242

Wiskott-Aldrich syndrome (WAS) 242

Grand Total 6162

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Database Query Requests Received in 2016

35 Registry Queries were received in 2016. They are grouped by study population as follows:

Study Population # of Query Requests

Ataxia Telangiectasia 1

CVID 10

CGD 1

DiGeorge Syndrome 2

General Registry 6

Hyper IgE 1

IVIG – Related 2

LAD 1

Quality of Life 1

SCID 2

Symptom - Specific 7

TOTAL 2016 35

The registry queries in full can be found below.

1. Are the CNS and lung abnormalities observed in ADA deficient patients are caused by metabolic abnormalities of the underlying disorder rather than complications? Would continuation of enzyme replacement therapy after HSCT or GT improve long-term outcomes?

2. What is the age of diagnosis for PIDD in both children and adults? I would like to also know the total number of current patients in the registry.

3. What are the age range of patients with PID, and to what age are diagnosed? 4. What are the similarities between USIDNET registrants with CVID and my specific cohort at MGH

in regards to immune phenotype and outcomes? 5. What are different biomarkers and symptoms which associated with WHIM? Also interested in

any information on genetic linkages and family history. 6. What are the clinical characteristics of primary immunodeficiency of unknown etiology? 7. What is the prevalence of CMV viremia in patients with primary immunodeficiency? Investigating

the specific types of PI involving susceptibility to CMV, end-organ disease due to CMV, types of treatments administered, and rates of and mortality attributed to CMV?

8. What are different biomarkers and symptoms which are associated with Warts? Investigating information on genetic linkages and family history.

9. What is the relationship between CVID and gastrointestinal conditions? 10. What is the relationship between respiratory issues and CVID? 11. What are the types of autoimmunity reported with CVID, and what is prevalence of each? Do

specific types of autoimmunity occur tend to occur together? Which types tend to occur after a diagnosis is made and IVIG is initiated?

12. Developing a machine learning system to assist clinical diagnosis of primary immunodeficiencies 13. What is the prevalence of autoimmune manifestations associated with PID diseases? 14. What are infectious and noninfectious complications of patients with hyper IgE syndrome? 15. Multivariate analysis of clinical factors that associated with increase rate of infectious and non-

infection complications in a cohort of patients with CVID

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16. What is the relationship between environmental toxin exposure and the rate of infections in patients with primary immunodeficiency?

17. What is the relationship between IVIG products and RSV for treatment of patients diagnosed with primary immune deficiency diseases, or PIDD?

18. What is the prevalence of LAD-I in the USIDNET registry? 19. What is the role of IG replacement in management of CVID patient's autoimmune disorders? 20. I am looking for data that I can use for a research project for a course in Biostatistics at Emory. I

will investigate the relationship between various continuous and categorical variables using SAS. 21. What are the types, frequencies, and distribution of pulmonary disease in patients with specific

categories of PI? We will characterize risk factors associated with the development of pulmonary disease in patients with PIDs. We are interested in determining the effect of pulmonary disease on quality of life in this population

22. What is the frequency of allergic respiratory disease among those with B cell defects that affect class-switching, quantitative, or qualitative production of immunoglobulins?

23. Do more patients with CVID have lung disease as compared to patients with XLA? Is there a difference in type of lung disease in patients with CVID versus XLA?

24. More precisely define peripheral B cell developmental defects and get some cues about its role in mature B cell antibody production function. We want to analyze TACI in peripheral B cells.

25. Does the use of IG replacement therapy in patients with 22q11 deletion syndrome correlated to an improved quality of life? What other factors could attribute to the decision to use IVIG?

26. What are clinical outcomes for individuals with primary T cell immunodeficiencies (e.g. SCID, Omenn Syndrome, DiGeorge Syndrome), specifically exploring outcomes for patients experiencing intracellular bacterial invasions?

27. I am trying to educate others early regarding trial to fight HIV. 28. What is the relationship between lupus and fibromyalgia? 29. We seek to enhance the understanding of PNP deficiency by analyzing key clinical and laboratory

characteristics of a cohort of patients. Specifically, we aim to describe the immune deficiencies most evident in patients with PNP deficiency, associated autoimmune and neurological conditions, and the treatments and outcomes for these patients.

30. What is the change in patients’ psychosocial perspectives as a result of treatment of PIDD with commercially available biologic therapies delivered through the subcutaneous route?

31. Completing a study comparing clinical phenotypes of pediatric-diagnosed CVID versus adult-diagnosed CVID in the USIDNET population. Specifically, we are interested in comparing the rates of infection, autoimmunity, and other co-morbidities between early-onset and adult CVID.

32. What is the frequency and severity of GI manifestations in CVID patients? We seek to provide a picture of the GI disease within this cohort including demographics, immunologic parameters, medical complications, both infectious and non-infectious, pathology, and treatments.

33. Looking for clinical descriptions and treatment outcomes for patients with 22qll.2 Del syndrome with extensive lymphadenopathy and abnormal RO/RA frequency ratios.

34. We aim to compare morbidity, mortality, and quality of life in patients with chronic granulomatous disease (CGD) treated with medical management alone, stem cell transplant (SCT), and gene therapy.

35. Assessment of infection, vaccination, growth, nutrition, endocrine (ovarian function) in patients with Ataxia Telangiectasia.

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Methods for Effective Patient Recruitment

Recruitment methods for the USIDNET in 2016 centered heavily on electronic consent, which is

approved for use to enroll patients through the IDF-ePHR as a part of the PI CONNECT project,

which is funded through PCORI:

Web Methods

An electronic consent* was approved and has been in use as a part of the PI CONNECT program since September of 2014.

Participants can consent with just a few clicks rather than the lengthy paper process.

USIDNET must still contact physicians for release of patient data for entry

To date, over 1910 patients have enrolled into USIDNET through this method.

Encourage the physicians and the community to promote PI CONNECT and the electronic consent process to their patients.

Clinical Immunology Conferences

USIDNET Staff attended AAAAI and CIS this year, where they answered questions from researchers, physicians, and other professionals related to the registry.

The most important tool at these meetings is the recruitment of new enrolling sites and physicians who can register their patients and promote patient engagement.

Physician Methods

Increased Physician outreach from the USIDNET Steering Committee during conferences, scholar programs, and mentoring

Referrals from the current enrolling Investigators and sites to accrue new sites

Increasing the amount of reimbursement available to enrolling physicians has sparked an uptick in new patients from our enrolling sites.

Print and Social Media Methods

Investigator Newsletters to the enrolling institutions to keep them informed about the progress of the registry, accrual, and new ideas and innovations to encourage more interaction/dialogue between the sites and USIDNET

Developed new Patient Information Cards that provide a clear, concise summary of the study / registry objectives.

Increased USIDNET activity and impact on Facebook, Twitter, and LinkedIn

19


USIDNET Social Media

The continued social media presence for USIDNET will effectively promote awareness of the Registry and all of USIDNET’s educational programs.

Follow us on Social Media and visit our website!

https://www.facebook.com/USIDNET

https://twitter.com/usidnet

http://usidnet.org/

https://www.facebook.com/ImmuneDeficiencyFoundation

https://twitter.com/IDFCommunity

https://instagram.com/idfcommunity/

http://primaryimmune.org/

https://www.facebook.com/USIDNET

https://twitter.com/usidnet

http://usidnet.org/

https://www.facebook.com/ImmuneDeficiencyFoundation

https://twitter.com/IDFCommunity

https://instagram.com/idfcommunity/

http://primaryimmune.org/

20


PI CONNECT: Merging the IDF ePHR with USIDNET Patient Registry

Background In April 2013 the Patient Centered Outcomes Research Institute (PCORI) released a Public Funding Announcement seeking to support new or existing Patient Powered Research Networks (PPRN) that would help further PCORI’s mission to conduct comparative effective research. IDF submitted a Letter of Intent in June 2013 that sought to create a new network between the eHealth Record and USIDNET – termed PI CONNECT. After submitting a full application detailing the project, IDF was awarded an 18-month contract to develop and expand the PI CONNECT network, with Dr. Kate Sullivan serving as Principal Investigator

Overview & Goal The PI CONNECT network connects the IDF ePHR, the electronic personal health record designed for the PI community, with USIDNET, the United States Immunodeficiency Network, a patient-consented registry. The IDF ePHR acts as a portal with the ability to electronically consent patients into the USIDNET Registry. The ePHR syncs with other EMRs and sources of clinical data. Patients can upload their medical information, either manually or through the sync capabilities, into the IDF ePHR, as well as provide QOL data through the PROMIS 29 survey. This information can be shared electronically with the USIDNET Registry. Once shared with USIDNET, all data is tagged with its respective source: patient reported vs. electronic transfer through other EMR, etc. A major goal of PI CONNECT is to connect researchers and patients. The PI CONNECT Research Forum is an online discussion service that allows patients a “seat at the research table” by allowing one on one and group discussions surrounding research topics in PI. Achievements

PI CONNECT launched in September of 2014.

By August of 2015, over 1500 people enrolled in PI CONNECT, and in turn, the USIDNET Registry

In February 2015, PI CONNECT Research Forum launched and Physician Engagement Committee (PEC) was formed to promote discussion between physicians and patients on the Forum

In November 2015, the PROMIS 29 QOL survey (NIH) was made available to PI CONNECT participants through the IDF ePHR

August 2015: IDF received Phase II funding from PCORI funding PI CONNECT for 3 more years! o The Phase II award allots $71,000 for USIDNET Registry upgrades

New, more vibrant, PI CONNECT community page launched in October 2016

IDF hosted 2 webinars, for PI CONNECT Participants o Women’s Health Issues in PI

o Emotional Health in PI

IDF released a spring and autumn PROMIS-29 with instant graphical feedback score in 2016.

o PROMIS Pediatric Global Health Survey implemented

ePHR was translated into Spanish in 2016, to reach a larger audience

o Also, translation of PI CONNECT & ePHR promo cards into Spanish

IDF initiated the “Fever Study” to be continued in 2017

In 2016, Quarterly Research Specific e-newsletters were sent to keep PI CONNECT members

informed

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PICONNECT ENROLLMENT STATISTICS

As of January 1, 2017, the total PICONNECT enrollment from all sources is 1,910.

These patients may have available data regarding:

Symptoms

Infusions

Vital Signs

PROMIS quality of life measures

At minimum, we have the following information on these participants:

Self-identified Primary Immunodeficiency Diagnosis

Gender

Race / Ethnicity

Age

There are currently 383* participants for whom we have clinically-verified data in USIDNET, including:

Clinical Primary Immunodeficiency Diagnosis

Information from clinical encounters

Information from laboratory reports *Participants are asked to complete an “Authorization for Disclosure of Health Information”, which allows USIDNET to acquire clinical data to enter in the registry. As more participants complete this form, these numbers will increase.

Patient Reported Clinician Confirmed Total

Agammaglobulinemia 46 17 63

ALPS 1 1

Antibody defect 1312 328 1639

Auto-inflammatory disease 1 1

Chronic granulomatous disease 12 6 18

Class switch defect 7 3 10

Complement deficiency 26 1 27

DNA repair 1 1

HLH 2 2

Hyper-IgE Syndrome 10 1 11

Innate immune deficiency 11 1 12

Mucocutaneous candidiasis 2 2

Neutrophil Disorders (non CGD) 2 1 3

SCID/CID 13 21 34

Thymic defect 1 1

WAS 1 3 4

Unclassified Immune Deficiency 60 60

Awaiting PID Confirmation 21 21

Grand Total 1527 383 1910

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PROMIS QUALITY OF LIFE SURVEY

PROMIS stands for Patient Reported Outcome Measurement Information System. Patient-reported

outcome (PRO) measures use answers that patients provide to produce numeric values, which indicate

states of wellbeing or suffering, as well as ability or lack of ability to function.

The NIH funded leading PRO and clinical investigators to develop a "psychometrically validated, dynamic

system to measure PROs efficiently in study participants with a wide range of chronic diseases and

demographic characteristics." The PROMIS initiative is part of the NIH goal to develop systems to

support NIH-funded research supported by all of its institutes and centers. PROMIS measures cover

physical, mental, and social health and can be used across chronic conditions.

PROMIS consists of three areas:

1. PRO Measure Development Standards: PROMIS stands for a particular set of methods used to

develop PRO measures. This methodology was developed by leading PRO researchers from

across the country and can be used as a model for future PRO development

2. PRO Measures: PROMIS used this methodology to create a large number of PRO measures of

health in multiple languages, for adults and children.

3. PRO Administration Software: PROMIS developed software, called "Assessment Center" to

facilitate using these new PRO measures with patients.

The PROMIS survey is available to users of the IDF ePHR with surveys released every Spring and Fall. To

date, 463 users have completed the PROMIS survey. Of these, 134 users are also PICONNECT

participants with clinical data in the USIDNET registry. Below you will find a diagnostic breakdown of

survey participants.

Diagnosis Total

Agammaglobulinemia 7

ALPS 1

Antibody defect 416

Class switch defect 1

Complement deficiency 2

Innate immune deficiency 2

SCID/CID 5

Unclassified Immune Deficiency 29

Grand Total 463

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Each person who consents to be a part of PI CONNECT is also consenting to join the USIDNET Registry. The consenting process is electronic has been approved by the SAIRB. Below is the text of the online consent:

What is PI CONNECT?

PI CONNECT is a tool designed to directly connect patients to research being conducted in the field of primary immunodeficiency (PI) diseases.

By joining PI CONNECT, you agree that the information you enter in your IDF e Personal HealthRecord (ePHR) will be shared with the United States Immunodeficiency Network (USIDNET). USIDNET is an established registry containing medical data on over 3600 patients with PI. Combining your information with USIDNET will help provide the most complete picture of your health. Physicians and researchers use what’s known as “de-identified” data, which means it cannot be traced back to you, from the registry to gain a better understanding of PI diseases, their outcomes, and treatments.

By joining PI CONNECT, you allow us to:

Store the data from your ePHR in the USIDNET Registry.

Combine the information you enter with medical information provided by your physician.

Share your de-identified data with researchers to advance the knowledge and treatment of PI.

What do we promise you?

We promise to safeguard your privacy. While agreeing to participate in PI CONNECT does not involve any physical risk, we know that the risk of loss of privacy is a concern for our patients. It is for us as well, so we take the following steps to ensure your data remains safe and private.

Only administrators will have access to identifying information such as your name and address.

We will only share de-identified data with researchers.

We will never give your contact information to an outside entity without your consent.

We will notify you immediately if there is ever a breach in your privacy.

You will always have the opportunity to remove yourself from PI CONNECT at any time.

Are there any benefits for me?

Of course contributing to research ensures better care in the future, and you can feel really great about that, but PI CONNECT provides even more value by connecting you directly to the research. You will be given access to an exclusive PI CONNECT research forum where you will be able to:

See research questions as they’re posed and offer your opinions about them.

Propose your own research questions that matter to you.

Track your own data and see how you compare to others with the same disease.

Have your ideas heard and translate them into actions!

What do I do?

You have already taken the first step by creating an IDF e Personal HealthRecord account. After indicating that you want to participate in PI CONNECT, you just continue to manage your health information in your ePHR, and we’ll take it from there. We will combine the information from your ePHR account with information obtained from your physician and add it all to the USIDNET Registry.

You may hear from us occasionally:

We will periodically send a reminder to ask you to update your ePHR.

We will alert you to specific research opportunities that become available.

If you have any questions about your involvement in PI CONNECT please contact Dr. Ramsay L Fuleihan of the Immune Deficiency Foundation at 866-939-7568 or 443-632-2556.

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What are my rights?

Participation in PI Connect, as with any research, is completely voluntary. You have the right to stop participating at any time. Know that you can choose not to participate now or even in the future, and it will not affect your medical treatment or access to care in any way.

Should you have questions about your rights as a research participant, or if you have concerns regarding this research study for which you would rather speak to someone other than our staff, you can contact Schulman Associates Institutional Review Board, Inc. toll free at 1-888-557-2472 during business hours Monday – Friday 8:00 a.m. to 6:00 p.m EST.

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Specific Aims for USIDNET: “Resources to Assist Investigations in Primary Immunodeficiency Diseases”

Specific Aim 1: Extend the scope, enrollment and utilization of the USIDNET Registry. The Registry

contains extensive clinical and laboratory data on >4000 subjects with PIDD, collected using a core form

for data common to all immune disorders as well as disease-specific forms designed by our expert

subcommittees. To extend this resource we will:

Aim 1a: Enroll more patients in all categories of the Registry, collect longitudinal data, develop

additional PIDD-specific forms, and further define patient outcomes using Quality of Life indicators. The

advent of newborn screening for severe combined immunodeficiency (SCID) and other disorders of

insufficient circulating naïve T cells requires new forms to record etiologies and trajectories of the

affected infants.

Aim 1b: Expand the use of this Registry to provide organization and support for selected observational

studies of high value to the patient community. Provide answers to a range of questions, stimulate

research collaborations to enhance global understanding of these defects.

Aim 1c: Engage the patient community directly and link with the eHealthRecord established by the IDF,

and funded by the Patient-Centered Outcomes Research Institute. Encourage patient participation by

new means.

Aim 1d: Increase collaborations and data sharing between the USIDNET Registry and other NIH funded

programs on PIDD: the Center for International Blood and Marrow Transplant Research (CIBMTR), the

Primary Immune Deficiency Treatment Consortium (PIDTC).

Specific Aim 2: Maintain and expand the current Repository of cell lines and other rare materials, to make

available unique resources and foster collaborative basic and translational PIDD research.

Specific Aim 3: Provide intensive training and educational opportunities to recruit physician-scientists to

careers in PIDD, create unique training experiences, and encourage collaborative research. We will

develop educational materials for physicians and basic researchers in allied fields and establish new

venues for promoting PIDD research in the United States.

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USIDNET Events of 2016

January Annual USIDNET Face-to-face Rockville, MD Jan. 29-30

February USIDNET launches Registry Statistics Webpage Towson, MD Feb. 18

Site Visit for Data Entry Assistance Boston, MA Feb. 29

March FILL Program launched Towson, MD March 1

AAAAI Annual Meeting Los Angeles, CA March 3

April CIS Annual Meeting Boston, MA April 14

May PROMIS 29 Survey launched through IDF ePHR Towson, MD May 1

IDF PI CONNECT Webinar: Women's Health Issues & PI Towson, MD May 12

July USIDNET Registry protocol renewed through SAIRB Towson, MD July 23

Site Visit for Data Entry Assistance Salt Lake City, UT July 18

October IDF launches PI CONNECT landing webpage Towson, MD October 11

November USIDNET launches PI CONNECT Statistics Webpage Towson, MD November 8

PROMIS 29 Survey launched through IDF ePHR Towson, MD November 1

IDF PI CONNECT Webinar: Emotional Health in PI Towson, MD November 2

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Educational Resources

USIDNET Travel Grants

Senior fellows and junior faculty are seldom able to attend high-level meetings that concentrate on PIDD

due to restricted travel funds. This is especially true for international meetings. USIDNET awards a small

number of travel grants to a few highly qualified junior faculty or committed senior fellows to attend

focused PIDD meetings. A committee reviews a career statement by applicants, a summary of

credentials, letters from mentors or program heads for this highly competitive award, which usually

includes the need for an accepted abstract.

In 2016, USIDNET awarded 8 Travel Grants to support travel for fellows and junior faculty to the Clinical

Immunology Society annual meeting. The recipients were:

Alberto Antonio, MD

Jocelyn Farmer, MD, PhD

Joel Gallagher, MD, FAAP

Joud Hajjar, MD

Heather Hartman, MD

Atoosa Kouroush, MD, MPH

Iris Otani, MD

Edith Schussler, MD, PhD

The “Summer School” in Primary Immune Deficiency

The Summer School program is a collaboration with the Clinical Immunology Society (CIS) with the goal

of intensive training in PID for junior physicians. The 15th Summer School was held in 2016, and since

that event, there have been 369 participants of this program. Of the attendees, 215 were from US

training programs. The majority were from Allergy Immunology programs, but Fellows in Infectious

Diseases, Rheumatology, Hematology/Oncology and Gastroenterology have also been accepted.

USIDNET contributes $25,000 each year towards the funding of this program.

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IDF & USIDNET LeBien Visiting Professor Program

The LeBien Visiting Professor Program promotes knowledge about the diagnosis and treatment of

primary immunodeficiency diseases. Teaching hospitals throughout the United States may submit a

request for a leading clinical immunologist to lead Grand Rounds or present at other educational

activities; such as bedside rounds or house staff and/or medical residents’ conferences.

The benefits of the USIDNET/IDF's LeBien Visiting Professor Program include:

o Increasing knowledge of diagnosis and treatment of primary immunodeficiency diseases

o Expert clinical immunologists to lead grand rounds and other educational activities

o Available to teaching hospitals throughout the United States

o Professional medical educational materials to accompany the program

Date Institution/Location Professor

February 26, 2016 Medical College of Wisconsin Dr. Ochs

August 17-18, 2016 Altru Health Systems of North Dakota Dr. Fuleihan

October 18, 2016 Pheonix Children’s/Mayo Clinic Dr. Buckley

January 17-18, 2017 (scheduled) Beaumont Hospital-Royal Oak, Michigan TBA

February 2017 (scheduled) Marshall University Dr. Routes

March 2017 (scheduled) University of Texas Medical Branch Dr. Torgerson

September 2017 (scheduled) University of South Florida Dr. Malech

Visiting Immunology Scholars Program (VISP)

The Visiting Immunology Scholars Program (VISP) gives medical students, residents, and fellows the

opportunity to spend one to two weeks at a medical center with an active PIDD research program. This

provides the opportunity for awardees to gain firsthand experience in patient evaluation, treatment,

and pertinent laboratory techniques. At the end of each visit, the awardees submit an evaluation of

their experience at the visit site. This allows USIDNET to document program success, track knowledge

gained by the awardees, and collect suggestions/comments. Because this is a valuable learning

opportunity for interested applicants, we will continue to utilize the program to help increase their

knowledge of clinical diagnoses and treatments of PIDD, as well as cutting edge research.

In 2016:

Applicant Home Institution Visited Institution Done

Magdalena Grzyb McGill University Boston Children’s Yes

Gargi Patel Rutgers Johns Hopkins Yes

Sun-Mi Choi St Louis Children’s CHLA Yes

Ottavia Delmonte Boston Children’s Application Pending

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Changes Made to the USIDNET Website in 2016:

USIDNET Database Statistics: in response to increasing requests for basic aggregate data, registry

statistics are now publicly available on the USIDNET website. Statistics are updated every month to

reflect the current registry numbers

o Available Data: the statistics page contains aggregate data on the following Enrollment by disease category and diagnosis Enrollment by disease category and age Enrollment by state (in the United States of America) Enrollment by race and ethnicity Enrollment by gender

o Purpose: by publishing this data, USIDNET hopes to reduce the burden of query submission from two perspectives.

Know before you submit. Researchers who wish to submit a query on a specific disease, demographic, or age range can first reference the statistics page to determine whether current participant populations are sufficient to satisfy their question.

No need to submit for basic factoids. Researchers need not go through the formal query process to obtain basic aggregate data.

o The page can be found at: https://usidnet.org/usidnet-database-statistics/

PICONNECT Database Statistics: created to provide research-focused information about the PI

CONNECT program for interested investigators.

o Available Data: the page contains aggregate data on the following Total PICONNECT Enrollment Total participants with clinically-verified data Diagnosis breakdown of participants

o The page can be found at: https://usidnet.org/about-piconnect/

Authorization for Release of Medical Records: in 2016, USIDNET implemented an online

authorization form to obtain clinical records for participants. Previously, this form would be mailed

to participants with a self-addressed, self-stamped return envelope. Now, the form is available on

Docusign.com for participants to complete in real-time.

o Faster Turnaround: registry manager instantly has access to the completed form once a user electronically signs it.

o Cost-Effective: price of annual subscription to Docusign is significantly less than the price of sending out mass-mailings to participants.

https://usidnet.org/usidnet-database-statistics/

https://usidnet.org/about-piconnect/

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New Registry Platform: Redcap Cloud

Introduction.

REDCap Cloud is based on Vanderbilt University’s REDCap electronic data capture (EDC) technology and best

practices that have proven effective through more than a decade of development and deployment

experience with nearly 2000 Academic Research Centers. REDCap Cloud builds upon the academic version

with key features and enhanced modules. It provides end-to-end study support through a single, easy-to-use

interface that customers can use to manage and run Basic Research, Surveys, ePRO/eCOA, e-Consent, Patient

Registries, Clinical Care and all Phases of Clinical Trials.

Leveraging Academic REDCap.

REDCap Cloud has a number of Key Features similar to Academic REDCap including:

Project Templates – selection of Project Types pre-configured with appropriate CRFs and variables

Import Data Dictionary – Create CRFs offline in a CSV file and import.

Variable Options –Text, Numbers, Radio Buttons, Dates, Calculated Fields, Branching Logic

Data Import – Create multi-Subject, multi-CRF CSV file offline & import

Roles & Permissions – Create Roles & enable Permissions by Role by Module

Audit Logs – full record of data creation and changes, date/time-stamped and user / IP address

Send it – Secure transfer of large / sensitive files up to 500MB

API Tokens for Web Service interfaces to import and/or export data from/to other apps.

Data Quality Tools – Variable Edit Checks, Data Comparison, Queries Workflow

Data Extract Tools – Data Sets, Casebooks, Reports

REDCap Cloud Enhanced Features & Modules

Created a new SaaS platform with license fees inclusive of Hosting and Technical Support; a new UI, and

enhanced and added to the features to create a commercial EDC application.

Regulatory Compliance – In the USA, CFR Part 11 and HIPAA, and in the EU, Annex 11

Language Options – Enable Global Studies to be conducted in local User Languages – including

Chinese, Japanese, Arabic, Spanish, German

ELearning module –user access to REDCap Cloud only post successful completion of a locally

configured ELearning assessment

Configure CRFs at individual Event level – optional CRF Version select, CRF site specific option,

Surveys – Enable CRFs as Surveys and configure and automate Survey launches

Mobile Apps for Offline Data Entry –use offline on tablets both Android and IoS

Annotated CRFs – standard field naming conventions required for submission of forms to FDA

Personal Health Information (PHI) – Option to auto-encrypt variables with PHI in the database using

256-bit technology (100% HIPAA Compliant)

Flexible Event Creation – Adding Repeating Events e.g. Adverse Events

Subject Screening Option at Enrolment – Conditions & Eligibility Criteria met?

Medical Coding API – auto-linking CRF medical data descriptions to standard medical dictionary terms

to achieve data consistency

Enhanced Security Features – All access in the system is tracked; who logged into the system, date and

time of the login, the IP address of the connection as well as failed logins.

Audit Trail: The REDCap Cloud system also has a robust audit trail that shows all changes to any

records within the system. Full Audit Logging of data/time/user access

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Changes Made to the USIDNET Diagnosis List in 2016:

Note: diseases listed in blue are new additions to the disease list.

Category New Preferred Name Genetic Defect

Agamma-globulinemia

Agammaglobulinemia of unknown cause or unlisted gene defect

BLNK deficiency BLNK

BTK deficiency, X-linked agammaglobulinemia (XLA) BTK

E47 transcription factor deficiency TCF3;

Ig alpha deficiency (CD79A) CD79a

Ig beta deficiency (CD79B) CD79b

l5 deficiency IGLL1

m heavy chain deficiency IGHM

PI3KR1 deficiency (AR)-agammaglobulinemia PIK3R1

ALPS

ALPS, unknown gene defect

ALPS-Caspase 8 CASP8

ALPS-Caspase10 CASP10

ALPS-FAS TNFRSF6

ALPS-FASLG TNFSF6

FADD deficiency FADD

PRKC deficiency PRKCD

Antibody defect

BAFF receptor deficiency TNFRSF13C (BAFF-R)

CARD 11 GOF (BENTA) CARD11

CD19 deficiency CD19;

CD20 deficiency CD20



Common variable immune deficiency with no gene defect specified

(CVID)

Hypogammaglobulinemia of unknown cause or unlisted gene defect

Ig heavy chain mutations and deletions DUP14q32

IgA Deficiency

IgG subclass deficiency

IgG subclass deficiency with IgA deficiency

Igk deficiency Kappa constant gene

IKAROS deficiency IKZF1

IRF2BP2 deficiency IRF2BP2

k chain deficiency IGKC

Mannosyl-oligosaccharide glucosidase deficiency MOGS (GCS1)

NFKB1 deficiency NFKB1

NFKB2 deficiency NFKB2

PI3K-d GOF PIK3CD

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Antibody defect

PI3KR1 deficiency (AD)-hypogammaglobulinemia PIK3R1

PTEN Hamartoma syndrome PTEN

Roifman Syndrome RNU4ATAC

Secondary hypogammaglobulinemia

Specific antibody deficiency with normal Ig concentrations and normal

numbers of B cells

TACI deficiency TNFRSF13B (TACI)

Thymoma with Immune deficiency (Good syndrome)

Transient hypogammaglobulinemia of infancy with normal numbers of

B cells

TRNT1 deficiency TRNT1

TTC37 deficiency TTC37

TWEAK TWEAK (TNFSF12)

Auto-inflammatory disease

A20 haplosufficiency TNFAIP3

ADAM17 deletion ADAM17

Autoinflammatory disease, unknown defect

Blau syndrome NOD2 (CARD15)

CAMPS (CARD14 mediated psoriasis ) CARD14

CANDLE (chronic atypical neutrophilic dermatitis with lipodystrophy) PSMB8

Cherubism SH3BP2

Chronic recurrent multifocal osteomyelitis and congenital

dyserythropoietic anemia (Majeed syndrome) LPIN2

CIAS1 disorders NLRP3 (NALP3, CIAS1,

PYPAF1)

COPA defect COPA

DIRA (Deficiency of the Interleukin 1 Receptor Antagonist) IL1RN

DITRA – Deficiency of IL-36 receptor antagonist IL36RN

Familial Mediterranean Fever MEFV

Mevalonate kinase deficiency (Hyper IgD syndrome) MVK

NLRC4-MAS (macrophage activating syndrome) NLRC4

NLRP12 GOF (Familial cold urticaria) NLRP12

PLAID (PLCg2 associated antibody deficiency & immune dysregulation) PLCG2

Pyogenic sterile arthritis, pyoderma gangrenosum, acne (PAPA)

syndrome PSTPIP1 (C2BP1)

SLC29A3 mutation SLC29A3

TNF receptor-associated periodic syndrome (TRAPS) TNFRSF1A

33


Chronic granulomatous disease

Abnormal neutrophil killing unknown defect

Autosomal recessive CGD – p22 phox deficiency (CYBA) CYBA

Autosomal recessive CGD – p40 phox deficiency (NCF3) NCF4



X-linked CGD - gp91 phox deficiency (CYBB) CYBB

Class switch defect

CD40 deficiency CD40 (TNFRSF5)

CD40L deficiency CD40LG

AID deficiency AICDA

Hyper IgM due to uncertain or unlisted cause

INO80 INO80

MSH6 MSH6

UNG deficiency UNG

Complement deficiency

C1 inhibitor deficiency SERPING1

C1q deficiency C1QA

C1r deficiency C1R

C1s deficiency C1S

C2 deficiency C2

C3 deficiency (LOF) C3

C3 GOF C3

C4 deficiency C4A

C5 deficiency C5

C6 deficiency C6

C7 deficiency C7

C8 a deficiency C8A

C8 a-g deficiency NB- alpha-gamma C8A, C8G

C8b deficiency C8B:

C9 deficiency C9

Complement deficiency due to uncertain or unlisted cause

Complement Receptor 3 (CR3) deficiency ITGAM

Factor B CFB

Factor D deficiency CFD

Factor H deficiency CFH

Factor H –related protein deficiencies CFHR1-5

Factor I deficiency CFI:

Ficolin 3 deficiency FCN3

MASP2 deficiency MASP2

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Complement deficiency

Membrane Attack Complex Inhibitor (CD59) deficiency CD59

Membrane Cofactor Protein (CD46) deficiency CD46

Properdin deficiency CFP:

Thrombomodulin THBD

DNA repair

Ataxia-telangiectasia ATM

Ataxia-telangiectasia-like disease (ATLD) MRE11A

Bloom Syndrome BLM ( RECQL3)

Immunodeficiency with centromeric instability and facial anomalies

(ICF1) DNMT3B


(ICF2) ZBTB24


(ICF3) CDCA7


(ICF4) HELLS

Ligase I deficiency LIG1

MCM4 deficiency MCM4

Nijmegen breakage syndrome NBS1

PMS2 Deficiency PMS2

RNF168 deficiency RNF168

Dyskeratosis congenita

AD/AR -DKC due to TPP1 deficiency TPP1

AD-DKC due to TERC deficiency TERC

AD-DKC due to TERT deficiency TERT

AD-DKC due to TINF2 deficiency TINF2

AR-DKC due to nucleolar protein family A member 3 (NHP3) or

NOP10 deficiency NOLA3 (NOP10 PCFT)

AR-DKC due to DCLRE1B deficiency DCLRE1B/

SNM1/APOLLO:

AR-DKC due to nucleolar protein family A member 2 (NHP2)

deficiency NOLA2 (NHP2)

AR-DKC due to PARN deficiency PARN

AR-DKC due to regulator of telomere elongation (RTEL1) deficiency RTEL1

Dyskeratosis congenita, unknown gene defect

XL-DKC due to Dyskerin deficiency DKC1

HLH

Chediak-Higashi syndrome LYST

FAAP24 deficiency FAAP24

Griscelli syndrome, type2 RAB27A

Hemophagocytic syndrome (HLH), unknown defect

Hermansky-Pudlak syndrome, type 2 AP3B1

Hermansky-Pudlak syndrome, type 9 PLDN

Perforin deficiency (FHL2) PRF1

35


HLH

SH2D1A deficiency (XLP1) SH2D1A

STXBP2 / Munc18-2 deficiency (FHL5) STXBP2

Syntaxin 11 deficiency, (FHL4) STX11

UNC13D / Munc13-4 deficiency (FHL3) UNC13D

XIAP deficiency (XLP2) XIAP (BIRC4 )

Hyper-IgE Syndrome

Hyper IgE syndrome AD STAT3 STAT3

Immune dysregulation

CD25 deficiency IL2RA

CTLA4 deficiency (ALPSV) CTLA4

HOIL1 deficiency HOIL1 (RBCK1)

HOIP deficiency HOIP1 (RNF31)

IL-10 deficiency IL10

IL-10Ra deficiency IL10RA

IL-10Rb deficiency IL10RB

IPEX, immune dysregulation, polyendocrinopathy, enteropathy X-

linked FOXP3

ITCH deficiency ITCH

NFAT5 haploinsufficiency NFAT5

Pleomorphic autoimmune disorder with unknown gene defect

STAT3 GOF mutations STAT3

Tripeptidyl-Peptidase II Deficiency TPP2

Innate immune deficiency

CD16 defect CD16

EVER1 deficiency TMC6

EVER2 deficiency TMC8

GATA2 deficiency (MonoMac) GATA2: loss of stem cells

IFNAR2 deficiency IFNAR2

IFN-g receptor 1 deficiency IFNGR1

IFN-g receptor 2 deficiency IFNGR2

IL-12 and IL-23 receptor b1 chain deficiency IL12RB1

IL-12p40 deficiency IL12B

IRAK-4 deficiency IRAK4

IRF3 Mutation IRF3

IRF7 deficiency IRF7

IRF8 Deficiency (AR and AD) IRF8

ISG15 deficiency ISG15

MKL1 deficiency MKL1

MYD88 deficiency MYD88

NK cell deficiency not specified

Predisposition to severe viral infections, unknown gene defect

RORc deficiency RORC

36


Innate immune deficiency

STAT1 deficiency (AD LOF) STAT1

STAT1 deficiency (AR) STAT1

STAT2 deficiency STAT2

Susceptibility to mycobacteria (MSMD) due to uncertain or unlisted

cause

TBK1 deficiency TBK1

TLR pathway abnormality, unknown defect

TLR3 deficiency TLR3

TRAF3 deficiency TRAF3

TRIF deficiency TRIF (TICAM1)

TYK2 deficiency TYK2

UNC93B1 deficiency UNC93B1

WHIM (Warts, Hypogammaglobulinemia, infections, Myelokathexis)

syndrome CXCR4

Interferonopathies

ADA2 deficiency CECR1

ADAR1 deficiency, AGS6 ADAR1

Interferonopathy, unknown defect

MDA 5 (IFIH1) Aicardi-Goutieres syndrome 7 (AGS7) IFIH1

RNASEH2A deficienc y, AGS4 RNASEH2A

RNASEH2B deficiency, AGS2 RNASEH2B

RNASEH2C deficiency, AGS3 RNASEH2C

SAMHD1 deficiency , AGS5 SAMHD1

Spondyloenchondro-dysplasia with immune dysregulation (SPENCD) ACP5

STING--associated vasculopathy, infantile-onset TMEM173

TREX1 deficiency, Aicardi-Goutieres syndrome 1 (AGS1) TREX1

USP18 Mutation USP18

X-linked reticulate pigmentary disorder POLA1

Mucocutaneous candidiasis

ACT1 deficiency ACT1 (TRAF3IP2)

APECED (APS-1), autoimmune polyendocrinopathy with candidiasis

and ectodermal dystrophy AIRE

CARD9 deficiency CARD9

IL-17F deficiency IL17F

IL-17RA deficiency IL17RA

IL-17RC deficiency IL17RC

Mucocutaneous candidiasis, unknown defect

STAT1 GOF STAT1

37


Neutrophil Disorders (non CGD)

3-Methylglutaconic aciduria CLPB

Abnormal neutrophil migration, unknown defect

b-actin deficiency ACTB

Barth Syndrome TAZ

Clericuzio syndrome Poikiloderma with neutropenia (C16orf57, USB1) C16orf57

Cohen syndrome COH1

ELANE (Elastase) deficiency (Severe congenital neutropenia 1) ELANE

G6PC3 deficiency (SCN4) G6PC3

G-CSF receptor deficiency CSF3R

GFI 1 deficiency (SCN2) GFI1

Glycogen storage disease type 1b G6PT1

HAX1 deficiency (SCN3/ Kostmann Disease) HAX1

JAGN1 deficiency JAGN1

Leukocyte adhesion deficiency type 1 (LAD1) ITGB2

Leukocyte adhesion deficiency type 2 (LAD2) SLC35C1

Leukocyte adhesion deficiency type 3 (LAD3) KINDLIN3

Localized juvenile periodontitis FPR1

Neutropenia, unknown defect

P14/LAMTOR2 deficiency ROBLD3 (LAMTOR2)

Papillon-Lefèvre Syndrome CTSC

Rac 2 deficiency RAC2

Shwachman-Diamond Syndrome SBDS

Specific granule deficiency C/EBPE

VPS45 deficiency (SCN5) VPS45

X-linked neutropenia/ myelodysplasia

Other Congenital Defects

Hennekam-lymphangiectasia-lymphedema syndrome CCBE1

Isolated congenital asplenia (ICA) RPSA

Pulmonary alveolar proteinosis CSF2RA

SCID / CID

Adenosine deaminase (ADA) deficiency ADA

BCL10 deficiency BCL10

BCL11A deficiency BCL11A

CARD11 deficiency CARD11

Cartilage hair hypoplasia (CHH) RMRP

CD27 deficiency CD27 (TNFRSF7)

CD3d deficiency CD3D

CD3e deficiency CD3E

CD3g deficiency CD3G.

CD3z deficiency CD3Z

38


SCID / CID

CD4 lymphopenia due to UNC119 deficiency (ICL) UNC119

CD45 deficiency PTPRC

CD8 deficiency CD8A.

Cernunnos/XLF deficiency Cernunnos

Combined immune deficiency with unknown or unlisted genetic cause

Comel-Netherton Syndrome SPINK5

Coronin-1A deficiency CORO1A

CTPS1 deficiency CTPS1

DCLRE1C (Artemis) deficiency ARTEMIS

DNA PKcs deficiency PRKDC

DOCK2 deficiency DOCK2

DOCK8 deficiency (Hyper-IgE) DOCK8

Ectodermal dysplasia with immunodeficiency due to unknown genetic

cause

EDA-ID IKBA GOF mutation (ectodermal dysplasia, immune deficiency IKBA (NFKIAB)

EDA-ID, NEMO /IKBKG deficiency (ectodermal dysplasia, immune

deficiency) NEMO (IKBKG)

Facial dysmorphism, immunodeficiency, livedo, short stature (FILS)

syndrome POLE1

gc deficiency (common gamma chain SCID, CD132 deficiency) IL2RG

HEBO deficiency ERCC6L2

Hepatic veno-occlusive disease with immunodeficiency (VODI) SP110

ICOS deficiency ICOS

IKBKB deficiency IKBKB

IL-21 deficiency IL21

IL-21R deficiency IL21R

IL7Ra deficiency IL7RA

Immune deficiency with syndromic features and unknown gene defect

Immunodeficiency with multiple intestinal atresias TTC7A

ITK deficiency ITK

JAK3 deficiency JAK3

Kabuki Syndrome due to KDM6A deficiency KDM6A

Kabuki Syndrome due to KMT2D deficiency KMT2D (MLL2)

LAT deficiency LAT

LCK deficiency LCK

Ligase IV deficiency LIG4

LRBA deficiency LRBA

MAGT1 deficiency (XMEN) MAGT1

MALT1 deficiency MALT1

Methylene-tetrahydrofolate dehydrogenase 1 (MTHFD1) MTHFD

39


SCID / CID

MHC class I deficiency (Bare lymphocyte syndrome type I) B2M , TAP1, TAP2, TAPBP

MHC class II deficiency group C (Bare lymphocyte syndrome type II RFX5

MHC class II deficiency group A (Bare lymphocyte syndrome type II) CIITA

MHC class II deficiency group B (Bare lymphocyte syndrome type II) RFXANK

MHC class II deficiency group D (Bare lymphocyte syndrome type II) RFXAP

Moesin deficiency MSN

MST1 deficiency STK4

NIK deficiency MAP3K14

Omenn syndrome, unknown gene defect

ORAI-I deficiency ORAI1

OX40 deficiency OX40 (TNFRSF4)

PGM3 deficiency PGM3

Purine nucleoside phosphorylase (PNP) deficiency PNP

RAG 1 deficiency RAG1

RAG 2 deficiency RAG2

Reticular dysgenesis AK2

RhoH Deficiency RHOH

Schimke Immunoosseous Dysplasia SMARCAL1

SCID, unknown gene defect

SLC46A1/PCFT deficiency causing hereditary folate malabsorbtion SLC46A1

STAT5b deficiency STAT5B

STIM1 deficiency STIM1

TCRα deficiency TRAC

Transcobalamin 2 (TCN2) deficiency TCN2

Transferrin receptor deficiency TFRC

Vici syndrome due to EPG5 deficiency EPG5

Winged helix deficiency (nude) SCID FOXN1

WIP deficiency WIPF1

ZAP-70 deficiency ZAP70

Thymic defect

CHARGE syndrome (CHD7) CHD7

CHARGE syndrome due to SEMA3E defects SEMA3E

CHARGE syndrome, unknown gene defect

Chromosome 22q11.2 deletion (22q11.2DEL) DEL22q11.2

DiGeorge/velocardiofacial syndrome, unknown defect

TBX1 deficiency TBX1

Unclassified Immune Deficiency

Immunodeficiency Unknown Cause

WAS Wiskott-Aldrich syndrome (WAS) WAS

40

Recent Publications from USIDNET Registry

1. Hernandez-Trujillo HS. et al Autoimmunity and Auto-Inflammation in X-Linked

Agammaglobulinemia. J Allergy Clin Immunol Clin Immunol. 2014;34(6):627-32

2. de la Morena MT, Nelson RP Jr. Recent advances for primary immune deficiency

diseases: a review. Clin Allergy Immunol 2014: 46:131

3. Shearer WT, et al Medical Advisory Committee of the IDF, Recommendations for live

viral and bacterial vaccines in immune deficient patients and their close contacts. J

Allergy Clin Immunol 2014: 133: 961

4. Sullivan KE, et al. USIDNET: A strategy to build a community of clinical immunologists. J

Clin Immunol. 2014: 34(4):428-35

5. Tuano KS, et al. Food allergy in patients with primary immune deficiency diseases:

prevalence in USIDNET. J Allergy Clin Immunol. 2015: 135, 273–275

6. Seeborg et al, Perceived Health in Patients with Primary Immune Deficiency. J Clin

Immunol 2015: 35, 638-650

7. Al-Herz W, et al; Combined immunodeficiency in the United States and Kuwait:

Comparison of patients' characteristics and molecular diagnosis. J Clin Immunol. 2015:

161:170-3.

8. Hotchko, Matthew. Forecast of the Global Immunoglobulin Market 2014-2023. Self

Pub. 2015

9. Leven, E, et al. (July 2016). Hyper IgM Syndrome: a Report from the USIDNET Registry.

J Clin Immunol. 36(5): 490-501.

10. Hartman H, et al. (25 Sept 2016). Lack of Clinical Hypersensitivity to Penicillin

Antibiotics in Common Variable Immunodeficiency. J Clin Immunol.

doi:10.1007/s10875-016-0353-7

11. Perelygina L, et al. (Nov 2016). Rubella persistence in epidermal keratinocytes and

granuloma M2 macrophages in patients with primary immunodeficiencies. J Clin

Immunol. 138(5): 1436-1439.

12. Hajjar J, et al. (In Press). Increased incidence of fatigue in patients with primary

immunodeficiency disorders: prevalence and associations within the United States

Immunodeficiency Network registry. J Clin Immunol.

41

Publication Submissions in Progress 2016

Cancer in Primary Immunodeficiency Diseases: An Analysis of Cancer Incidence in the United States Immune Deficiency Network (USIDNET) Registry

Purpose: in patients with confirmed PIDD diagnoses, there is a higher than expected incidence of cancer. This report will examine the clinical features of these patients, and the factors which may pre-dispose them to malignancy.

Authors: Paul C. Mayor, Kevin H. Eng, Kelly L. Singel, Scott I. Abrams, Kunle Odunsi1, Kirsten B. Moysich, Brahm H. Segal

Two Sides of the Same Coin: Pediatric-Onset and Adult-Onset Common Variable Immune Deficiency

Purpose: CVID is a complex, heterogeneous immune deficiency characterized by hypogammaglobulinemia, recurrent infections, and poor antibody response to vaccination. While antibiotics and immunoglobulin prophylaxis have significantly reduced infectious complications, non-infectious complications of autoimmunity, inflammatory lung disease, enteropathy, and malignancy remain of great concern. Previous studies have suggested that pediatric CVID patients are more severely affected by these complications than adults diagnosed later in life. We sought to identify the major complications in pediatric-diagnosed (ages 17 or younger) versus adult-diagnosed CVID (ages 18 or older).

Authors: Lauren A. Sanchez, M.D.1, Solrun Melkorka Maggadottir, M.D.1, Matthew S. Pantell, M.D.2, Patricia Lugar, M.D., M.S.3, Charlotte Cunningham Rundles, M.D., Ph.D.4, Kathleen E. Sullivan, M.D., Ph.D1 and the USIDNET Consortium. 1Division of Allergy and Immunology, Children’s Hospital of Philadelphia, Philadelphia, PA 19104 2Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143

Gastrointestinal Manifestations in X-linked Agammaglobulinemia

Authors: Sara Barmettler, MD1*, Iris M. Otani, MD1,2*, Jasmit Minhas, MD3, Roshini S. Abraham PhD4,

Yenhui Chang, MD, PhD5, Morna J. Dorsey2, MD, Zuhair K. Ballas, MD6, Francisco A. Bonilla, MD,

PhD7, Hans D. Ochs, MD8, Jolan E. Walter, MD, PhD1,5

42

Abstracts Accepted and Submitted in 2016

Using EMR Data Collections to Outline SCID Clinical

Phenotypes

Shradha Agarwal, MD, FAAAAI, Peter Sidi, Charlotte

Cunningham-Rundles, MD, PhD; Icahn School of Medicine

at Mount Sinai, New York, NY.

RATIONALE: SCID is a genetic disorder caused by

mutations in cellular and humoral immunity leading to

heterogeneous presentations. Early identification and

transplantation reduces morbidity and mortality as

demonstrated by improvement in immune function. We

compared three patient registries to dissect clinical

phenotypes of SCID.

METHODS: Using ICD code 279.2, three registries were

queried for patients with SCID. USIDNET (1997-2014)

included specialists entered data; SPARCS (2005-2010)

collected hospital data from NYS; HCUP (2009) collected

data from 103 US hospitals. Demographics and clinical

data for subjects under the age of 20 were extracted

utilizing databases’ reporting tools.

RESULTS: In all data sets there was predominance of males

with SCID (63%, 51%, 60%) and Caucasian subjects (53%,

54%, 41%). Pneumonia was the most common diagnosis

associated with SCID (17.8%, 18.9%, 11.1%). Other

diagnoses across registries: skin infections (10.5%, 10.9%,

0.73%), sepsis (4.0%, 5.1%, 6.8%), fever (7.3%, 2.3%), viral

(4.5%, 2.9%, 5.8%), sinusitis (7.4%, 1.7%, 1.7%), otitis

(9.1%, 1.1%, 0.87%). While USIDNET collected selected

fields, SPARCS and HCUP collate all ICD codes, including

numerous gastrointestinal, neurologic, allergic, nutritional,

failure-to-thrive, and endocrine codes. Within HCUP,

California had the most SCID related discharges followed

by Ohio, Texas, New York. 47% of admissions occurred by

age 2 (0yr-25.6%; 1yr-12.1%; 2yr-9.2%).

CONCLUSIONS: Data sets of EMRs are powerful resources

allowing the capture of global clinical data about rare

diseases. Contrasting the collection of selected data fields

(USIDNET) with other global medical collections (SPARCS,

HCUP) produces a more rounded clinical phenotype of rare

immune defects, across medical boundaries.

AAAAI 2016

Prevalence of Atopic Diseases in Patients with Humoral

Primary Immunodeficiency: A Comparison of a Single

Center and the US Immunodeficiency Network (USIDNET)

Alice Chau, MD1 , A Jongco, III, MD, PhD, MPH2,3, L Helfner,

MD4 , J Fagin, MD5 , V Bonagura, MD, FAAAAI2,6; 1 Dept of

Medicine, Hofstra North Shore, Manhasset, NY, 2 Feinstein

Institute for Medical Research, Manhasset, NY, 3 Division

of Allergy/Immunology Hofstra North Shore, Great Neck,

NY, 4 Division of Allergy/Immunology, Dept of Medicine

and Pediatrics, Hofstra North Shore, Great Neck, NY, 5

Allergy Immunology, ProHEALTH Care Associates, New

Hyde, NY, 6 Division of Allergy/Immunology at North Shore

Long Island Jewish Health System, Great Neck, NY.

RATIONALE: Humoral primary immunodeficiency diseases

arise from defects in B cell differentiation, maturation, and

class switch recombination. Nevertheless, a subset of

these patients demonstrate atopic disease with

corresponding elevated IgE. We characterized the

prevalence and kinds of atopic conditions present in two

distinct populations.

METHODS: We determined prevalence of IgE-mediated

atopic disease and immunologic characteristics of humoral

PIDD patients seen at an academic medical center

immunology clinic (retrospective chart review, 2001-2011)

and enrolled in the USIDNET Registry (queried 5/5/2015).

The following diagnoses were included: congenital

agammaglobulinemia (279.04), idiopathic agamma-

globulinemia (279.00), selective IgA deficiency (279.01),

IgG subclass deficiency (279.03), specific antibody

deficiency (279.19), and hyper IgM syndromes (279.05).

RESULTS: 65 of 92 clinic patients and 616 of 4087 registry

participants were included in analysis. The distribution of

PIDD diagnoses was as follows (clinic;USIDNET): 279.00

(32.0%; 2.3%), 279.01 (22.0%; 4.5%), 279.03 (0%; 1.9%),

279.04 (20.0%; 61.7%), 279.05 (3.0%; 23.9%), and 279.19

(23.0%; 5.8%). The distribution of atopic diagnoses were as

follows: allergic rhinitis(38.5%; 8.6%), asthma(28.6%;

43.6%), drug allergy(11.0%; 28.8%), eczema(6.6; 16.5%),

and food allergy(2.2%; 2.5%). ImmunoCAP or skin prick

testing and serum IgE values were available in 41 and 55

clinic patients, respectively, while serum IgE was

documented in 131 database patients. In both cohorts,

279.04 and 279.05 patients had the most number of

undetectable IgE.

CONCLUSIONS: Humoral PIDD patients can develop IgE-

mediated type 1 hypersensitivities, many with

documented serum IgE levels. The distribution of PIDD and

atopic diagnoses differ between the two populations. Both

registry and single center data are informative and do not

necessarily demonstrate similar trends.

AAAAI 2016

43

Body Weight and Infectious Outcomes in Patients with

Primary Immunodeficiency Diseases: Outcomes from

within the US Immunodeficiency Network (USIDNET)

Melanie A. Ruffner, MD, PhD1 , USIDNet2 . Kathleen E.

Sullivan, MD, PhD, FAAAAI1 ; 1 The Children’s Hospital of

Philadelphia, Philadelphia, PA, 2 USIDNET

RATIONALE: A growing body of evidence supports

complex role of body weight with infectious and

inflammatory disease outcomes. However, there have

been no studies to date examining body weight as a

modifying factor in primary immunodeficiency diseases

(PIDD). The goal of this study is to estimate prevalence of

obesity and underweight status in immunodeficient

patients, and to determine if body weight is associated

with a higher rate of infectious complications in patients

with PIDD.

METHODS: The USIDNET is a research consortium

established to advance understanding of PIDD. The

USIDNET database was queried for all patients with

complete height and weight information; patients without

this information were excluded. Additional demographic

and clinical information, including infectious and medical

complications were also obtained for each patient.

RESULTS: 512 adults (age>20) and 660 children (ages 2-20)

had complete BMI data. 4.1% of adults had BMI>40, 21.4%

had 40>BMI>30 and 5.7% were underweight with

BMI<18.5. 13% of pediatric patients had BMI>95 th

percentile (obese) and 7.1% with BMI<5 th percentile

(underweight). There were variable associations between

body weight and complications of PIDD within cohorts of

patients divided by diagnosis. For example, obesity was

associated with increased frequency of sepsis (12% vs 6%,

p=0.05) but not pneumonia in adults with CVID.

Conversely, in pediatric CVID patients, pneumonia was

associated more frequently in underweight subjects,

although this did not achieve significance (77% vs 45%,

norm weight vs 32% obese, p=0.07)

CONCLUSIONS: This retrospective data presents new

associations between body weight and PIDD and argues

for consideration of body weight in PIDD studies.

AAAAI 2016

Extra-Immunologic Manifestations of Common Variable

Immunodeficiency in Pediatric Versus Adult Patients

Lauren Sanchez, MD, MA1, Matthew Pantell, MD, MS2,

Solrun Maggadottir, MD1, Kathleen Sullivan, MD, PhD,

FAAAAI3, USIDNet4; 1Children’s Hospital of Philadelphia,

Philadelphia, PA, 2University of California, San Francisco,

San Francisco, CA, 3Children’s Hospital of Philadelphia,

Philadelphia, PA, 4U.S. Immunodeficiency Network.

RATIONALE: Common variable immunodeficiency (CVID) is

a primary immunodeficiency defined by

hypogammaglobulinemia, poor antibody response to

vaccinations, and frequent or chronic bacterial infections.

CVID has also been associated with autoimmunity,

increased risk of lymphoid malignancy,

enteropathy/colitis, and granulomatous disease. We

sought to define other extra-immunologic manifestations

in pediatric and adult patients with CVID.

METHODS: We utilized retrospective data made available

from the United States Immunodeficiency Network

(USIDNET). 231 pediatric patients (i.e. ≤17 years old) and

339 adult patients (i.e. ≥18 years old) were identified in

USIDNET with a diagnosis of CVID, and had at least one

documented clinical condition. Chi-squared testing was

used to compare conditions between pediatric and adult

patients.

RESULTS: Frequently reported extraimmunologic

manifestations in both pediatric and adult CVID patients

included non-infectious diarrhea (22.51% vs 28.61%,

respectively), fatigue (30.74% vs 38.64%),

gastroesophageal reflux disease (17.75% vs 23.01%) and

headaches (8.23% vs 14.75%). Frequently reported

conditions with clinically significant (p <0.05) enrichment

in adult CVID patients included aches/chronic pain (9.52%

vs 23.60%, p<0.001), arthralgia (10.82% vs 17.99%,

p=0.019), anxiety (1.73% vs 5.31%, p=0.029), depression

(6.49% vs 22.42%, p<0.001), hypothyroidism (3.03% vs

10.91%, p=0.001), non-lymphoid malignancy (2.60% vs

11.50%, p<0.001) and osteopenia (2.60% vs 7.96%,

p=0.007).

CONCLUSIONS: Chronic pain (“aches” and arthralgia),

anxiety, and depression are underappreciated but

frequently reported co-morbid conditions in CVID. Regular

screening for depression and anxiety in adult CVID patients

may be justified. Further research may be warranted to

understand how best to provide psychosocial supports to

both pediatric and adult patients with CVID.

AAAAI 2016

44

Clinical Characteristics and Diagnosis in Patients with

Predominantly Antibody Deficiencies: Baseline Features

of Patients Enrolled in The United States

Immunodeficiency Network (USIDNET) Registry

Albert O. Antonio, DO (Cohen Children's Medical Center of

New York, Hofstra Northwell Health School of Medicine)

Background: Disease registries improve our understanding

of primary immunodeficiencies.

Objective: We queried the US Immunodeficiency Network

(USIDNET) Registry to better understand the natural

history and clinical characteristics of agammaglobulinemic

and hypogammaglobulinemic registry subjects.

Design/Methods: This retrospective study included 409

humoral immunodeficient subjects enrolled from 2008 to

2015 (14.2% of total registrants). Pairwise association

between variables was assessed via the Mann-Whitney,

Fisher's exact, or incidence density ratio tests.

Results: Eleven specific diagnoses were represented. X-

linked agammaglobulinemia (85.8%) and

hypogammaglobulinemia of unknown cause (61.8%) were

the most prevalent. The sample was 69.2% male and

58.7% Caucasian. The two disease groups significantly

differed by gender, race, history of ≥1 infection, median

age of symptom onset and diagnosis (p<0.005 for each).

The hypogammaglobulinemia group had longer median

diagnostic delay (0.5 years; IQR: 0-2.7 vs. 3.0 years; IQR:

0.3-7.0) (p=0.0002). The two groups did not differ in

antibiotic prophylaxis use, number of antibiotic courses,

infection count and serious infection count.

Conclusions: Registries can reveal clinically relevant

differences between disease groups. This study highlights

some of the strengths and limitations of registry-based

research.

CIS 2016

Tertiary Care Patients with Common Variable Immune

Deficiency (CVID) Are at Similar Risk for Noninfectious

Complications: A Comparative Cohort Analysis Between

Partners-Affiliated Hospitals in Boston, MA and The

USIDNET National Registry.

Jocelyn Farmer, MD, PhD (Massachusetts General Hospital)

The epidemiology of CVID has been described almost

exclusively at large referral centers and centralized

databases such as the USIDNET. These data demonstrate

the morbidity of noninfectious sequelae, which occur in

the majority of patients with CVID. Our goal was to

establish the frequency and severity of noninfectious

sequelae at a large tertiary care center. We conducted a

retrospective cohort analysis of patients with CVID who

have been diagnosed or treated at Partners HealthCare

Network Hospitals in Boston, MA (including the

Massachusetts General Hospital and the Brigham and

Women’s Hospital, both of which are large tertiary care

centers but not referral centers for CVID). Our cohort of

approximately 180 CVID patients was comparable to the

USIDNET with regard to age at diagnosis, native

immunoglobulin levels, and overall complication rates,

although detailed analysis showed increased frequency of

asthma (46.5 vs. 32.7%), thyroid disease (11.2 vs. 0.9%),

and noninfectious rheumatologic complications (14.2 vs.

5.1%) in the Partners’ cohort. We also observed lack of

routine B cell maturation phenotyping (only 20%) and a

range of replacement trough IgG levels (899 +/- 252

mg/dL) in the Partners’ cohort. Future work will address

whether autoimmune disease development is significantly

related to immunoglobulin replacement dosing, B cell

phenotype, and/or novel screening markers.

CIS 2016

Increased Incidence of Fatigue in Primary

Immunodeficiency Disorders, Prevalence and

Associations within the USIDNET Registry.

Joud Hajjar, MD (Baylor College of Medicine)

Introduction: Primary Immunodeficiency (PI) patients

often report fatigue, yet it has not been studied in PI.

Fatigue affects 6-7.5% of healthy adults. The goal of this

study was to estimate the prevalence of fatigue in PI and

investigate its associated factors.

Methods: We performed a query of 2537 PI patients

registered in USIDNET to determine responses to the field

“fatigue” in the core registry. Demographics, immune

phenotype and comorbid conditions were compared

between fatigued and non-fatigued patients to identify

relevant associations. T-test, Chi-square, Fisher’s exact and

Wilcoxon rank sum tests were used to compare the 2

groups.

Results: Fatigue prevalence was 16.9% (95% CI: 15.5-18.5).

79% of fatigued patients had Primary Antibody Deficiency

(PAD). Fatigue was reported in 24.3% (95% CI: 22.1-26.7)

of PAD patients, compared to 7.8% (95% CI: 6.3-9.55) of

non-PAD. Prevalence of fatigue was the highest in CVID

(p<0.001). Fatigued patients were more likely to be

females, not on IVIG, had higher BMI, higher rate of

autoimmunity, hepatomegaly and granulomas, and lower

45

Absolute Lymphocyte, CD3, CD4, and CD8 counts

compared to non-fatigued (p<0.005-<0.001).

Conclusion: Our findings suggest that fatigue is over-

represented in PI patients. Prospective studies to estimate

prevalence, risk factors and fatigue etiology in PI are

warranted, so therapeutic interventions can be conceived.

CIS 2016

Hyper IgM Syndrome: A Report from the USIDNET

Registry

Emily Leven1, H Ochs, MD2, P Scholl3, R Buckley, MD4, R

Fuleihan, MD5, R Geha, MD6, C Cunningham7, F Bonilla, MD

PhD8, M Conley9, R Ferdman10, V Hernandez-Trujillo, MD11,

J Puck, MD12, K Sullivan, MD, PhD13, P Maffucci, BA14, M

Ramesh15 and C Cunningham-Rundles, MD, PhD14; 1Icahn

School of Medicine at Mount Sinai, New York, NY, 2Department of Pediatrics, University of Washington

School of Medicine, Seattle, WA, 3Boehringer Ingelheim

Pharmaceuticals, 4Division of Allergy and Immunology,

Duke University School of Medicine, Durham, NC, 5Division

of Allergy and Immunology and Jeffrey Modell Diagnostic

Center for Primary Immunodeficiencies, Dept of Pediatrics

and Dept of Pathology, Children’s Memorial Hospital,

Northwestern University Feinberg School of Medicine,

Chicago, IL, 6Immunology Division, Department of

Pediatrics, Boston Children's Hospital, Harvard Medical

School, Boston, MA, 7Department of Pediatrics, Duke

University Medical Center, Durham, NC, 8Medicine/Immunology, Boston Childrens Hospital,

Boston, MA, 9St. Giles Laboratory of Human Genetics of

Infectious Diseases, Rockefeller Branch, The Rockefeller

University, New York City, NY, 10Division of Clinical

Immunology and Allergy, Department of Pediatrics,

Children's Hospital Los Angeles, University of Southern

California, 11Allergy/ Immunology, Miami Children's

Hospital, Miami, FL, 12Pediatrics, University of California

San Francisco, San Francisco, CA, 13Children's Hospital of

Philadelphia, Philadelphia, PA, 14Division of Clinical

Immunology, Department of Medicine, Icahn School of

Medicine at Mount Sinai, New York, NY, 15Montefiore

Medical Center, New York City, NY

PURPOSE: The United States Immune Deficiency Network

(USIDNET) patient registry was used to characterize clinical

presentation, genetic mutations, immunologic phenotypes

and treatment practices in a large number of patients with

Hyper IgM Syndrome (HIGM).

METHODS: The USIDNET Registry was queried for all HIGM

patient data collected from Oct. 1992 to July 2015.

RESULTS: 52 physicians entered data for 145 HIGM

patients (131 male); 2,072 patient years were analyzed.

Median age at entry was 12 years (2 months – 62 yrs).

Causal mutations were recorded in 72 subjects; 68 were in

CD40L. 5% had autosomal recessive HIGM. 58 subjects

(40%) had normal serum IgM and 22 (15%) had normal

IgA. 91% of patients reported infection. Pulmonary, ear,

and sinus infections were most common. Pneumocystis

jiroveci was reported in 42% and Cryptosporidium in 6%.

41% had neutropenia. 78% experienced non-infectious

complications: chronic diarrhea (n=22), aphthous ulcers

(n=28), and neoplasms (n=8). 16 patients underwent

transplantation (13 hematopoietic marrow/stem cell, 3

solid organ). 13 were known to have died (median age =

14 yrs).

CONCLUSIONS: Analysis of the USIDNET Registry provides

data on common clinical features of this rare syndrome,

and in contrast with previously published data,

demonstrates longer survival times and reduced incidence

of respiratory tract complications and gastrointestinal

diseases.

CIS 2016

Inflammatory Bowel Disease in X-Linked

Agammaglobulinemia

Iris M Otani, MD (Massachusetts General Hospital)

Aside from infections, patients with X-linked

agammaglobulinemia (XLA) may present with autoimmune

or inflammatory complications. We follow a 71-year-old

patient initially diagnosed with Crohn’s disease at 35 years

of age and partially treated with prednisone and 5-amino

salicylates. In his 40s, for history of chronic lung disease,

he was investigated and diagnosed with

hypogammaglobulinemia and placed on intravenous Ig

(IVIG). Only recently, when his 3 year-old grandchild

presented with absent IgG, were both patients diagnosed

with XLA. Interestingly, while he continues to have mild

gastrointestinal (GI) complaints, he has not required active

treatment or hospitalization since starting IVIG

replacement.

IVIG therapy has recently been gaining recognition as a

potentially beneficial treatment for Crohn’s disease.

Possibly, IVIG use in the XLA patient population is

preventing progression of IBD. We queried the USIDNET

registry for patients with XLA and GI disease. Of 19

patients, eight (50%) had a history of a chronic GI

infection, 17 patients (89%) were treated with

immunoglobulin replacement therapy.

Immunomodulatory treatment for IBD was reported in

46

two cases, however 14 patients (73%) required parenteral

nutrition. Longitudinal studies are needed to investigate GI

pathology and progression of IBD in XLA patients and to

identify treatment strategies.

CIS 2016

Gastrointestinal Presentations in Patients with CVID

Edith Schussler, MD (Icahn School of Medicine Mount Sinai)

Rationale: Gastrointestinal symptoms are common in CVID

patients and often severe. We report clinical

characteristics of CVID patients registered in USIDNET.

Methods: The USIDNET Registry was queried for

information about CVID related GI disease.

Results: 413/889 (46%)CVID patients in the USIDNET

registry have had a GI condition 55% were female and

45%, male. Mean age at diagnosis of CVID was 26.3 yrs.

Immunoglobulins were (mg/dl): IgG mean 735, median

1134, range 7-2640, IgA mean 53.4, median 27, range 0-

716, IgM mean 66.1, median 37, range 0-1210. These

conditions included GE reflux (176), diarrhea (228),

abdominal pain (114), IBD (34), constipation (55),

colitis/enteritis (38), liver function abnormality (27),

malabsorption (24), hepatomegaly(22), celiac disease (11),

eosinophilic esophagitis (18), cirrhosis (10), autoimmune

hepatitis (3), appendicitis (10), aphthous ulcers (7),

protein losing enteropathy (3), intestinal nodular lymphoid

hyperplasia (5), fistula (5), obstruction (4), gall bladder

disease (5), gall stones (3), eosinophilic enteritis (3),

perianal ulceration (2), steatosis (1). 25 patients had

received TPN. 67 also had had another autoimmune

condition. There were 15 lymphomas, 4 leukemias and 11

other cancers reported in these subjects.

Conclusion: Common and rarer inflammatory GI

manifestations occur in CVID and targeted interventions

may be needed.

CIS 2016

Natural History of Children with Agammaglobulinemia

and Hypogammaglobulinemia: Baseline Features of

Patients Enrolled in the United States Immunodeficiency

Network (USIDNET)

Albert O. Antonio1, Marla L. Goldsmith2, Cristina P. Sison3

and Artemio M. Jongco4. 1Division of Neonatal-Perinatal

Medicine, Cohen Children's Medical Center of New York,

Hofstra North Shore-LIJ School of Medicine, New Hyde

Park, NY; 2United States Immunodeficiency Network,

Towson, MD; 3Feinstein Institute for Medical Research,

Hofstra North Shore-LIJ School of Medicine, Manhasset, NY

and 4Division of Allergy and Immunology, Cohen Children's

Medical Center of New York, Hofstra North Shore-LIJ

School of Medicine, New Hyde Park, NY.

BACKGROUND: Primary immune deficiency diseases

(PIDDs) comprise a heterogeneous group of rare diseases

caused by disorders of immune regulation and function.

Affected individuals have increased susceptibility to

recurrent infections, and may be predisposed to atopy or

autoimmunity or malignancy. We reviewed data on

patients with agammaglobulinemia and

hypogammaglobulinemia in the United States

Immunodeficiency Network (USIDNET) Registry, the

largest U.S. PIDD-centric registry, to examine the natural

history and characteristics of these patients.

OBJECTIVE: To describe the natural history and

characteristics of agammaglobulinemic or

hypogammaglobulinemic patients in the USIDNET registry.

DESIGN/METHODS: This retrospective study included data

from 274 subjects diagnosed with agammaglobulinemia

and hypogammaglobulinemia from 2008 to 2015,

representing 9.5% of the 2884 total PIDD registrants. Four

queries were submitted to determine the responses to

fields in the core registry form in order to generate

paralleled datasets regarding similarities in clinical

characteristics, immunologic status, genetic information

and, infectious/non−infectious conditions/outcomes. Data

were extracted using Boolean queries for specific data and

analyzed using Statistical Analysis System.

RESULTS: Nine specific diagnoses were represented in the

study population, with X-linked agammaglobulinemia

(187/201) and specific antibody deficiency with normal Ig

concentrations and normal numbers of B cells (35/73),

being the most prevalent reported agammaglobulinemia

and hypogammaglobulinemia respectively. The sample

was 82% (224/274) male. The large majority were

Caucasians (86.5%) followed by African Americans (10.4%).

Median age at symptom onset was two years (IQR: 0.5-

5)(n=126) and the median age at diagnosis was four years

(IQR: 1.5–19.2)(n=203). The median diagnostic delay was

one year (IQR: 0-5.5)(n=118).

CONCLUSIONS: We present the first broad consideration

and comparison of agammaglobulinemia and

hypogammaglobulinemia using the USIDNET registry.

Improved understanding of the natural history of these

under-diagnosed and under-reported diseases will

enhance awareness, raise physician suspicion for screening

and early detection, and reduce diagnostic delay to

facilitate timely intervention.

ESPR 2016

47

Immunoglobulin Management Approaches in American

Patients with Common Variable Immune Deficiency and

Autoimmunity

K. Kennedy (Philadelphia, PA), C. Cunningham-Rundles

(New York, NY), M. Morsheimer (Wilmington, DE)

INTRODUCTION: Common variable immune deficiency

(CVID) is a primary immune deficiency characterized by B

cell dysfunction and paucity of protective specific

antibodies. Autoimmunity, and commonly hematologic

cytopenias, is also a manifestation. Immunoglobulin

replacement therapy is the cornerstone of management;

treatment route and dose can be used to modulate the

frequency and severity of cytopenias. Typically IV

immunoglobulin administration (IVIG) at high doses is

required for immunomodulatory benefits, however

international experience suggests subcutaneous

administration at lower doses can also be successful. We

aim to summarize the American experience regarding

immunoglobulin route and dosing among CVID subjects

with autoimmunity.

METHODS: A USIDNET enrollment characteristic query of

1494 CVID patients revealed 105 cases with autoimmunity.

Variables assessed included sex, autoimmune disorder,

transfusion history, adjunctive immunomodulatory

medications, and immunoglobulin dose and administration

route. STATA performed descriptive statistics.

RESULTS: The majority were female (61%) and treated

with IVIG (72%). One third had cytopenias, most

commonly immune thrombocytopenic purpura (14.2%).

Nearly 80% with cytopenias received IVIG (300 to 1300

mg/kg/dose); 67% of these patients required

immunomodulatory medications and 18% required

transfusions. Approximately 20% with cytopenias were

treated with subcutaneous immunoglobulin (SCIG) (100-

150mg/kg/dose); 86% of these patients required

immunomodulatory medications and 42% required

transfusions.

CONCLUSION: Most American CVID patients with

cytopenias were managed with IVIG and had lower rates

of immunomodulatory medications and transfusions than

those on SCIG. There was a wide range of autoimmunity

noted in the cohort with the same preference for IVIG

noted for non-hematologic complications. Institutional-

level data is required to identify characteristics predictive

of success on SCIG.

ACAAI 2016

Cancer in Primary Immunodeficiency Diseases: An

Analysis of Cancer Incidence in the United States Immune

Deficiency Network (USIDNET) Registry.

Paul Mayor, Kevin H. Eng, Kelly L. Singel, Scott I Abrams,

Kirsten B. Moysich, Kunle Odunsi, Brahm H. Segal; Roswell

Park Cancer Institute, Buffalo, NY

Background: We reported the overall and site-specific

incidence of cancer in the United States Immune

Deficiency Network (USIDNET) Registry. We hypothesized

that patients with Primary Immunodeficiency Diseases will

have an increased incidence of cancer due to impaired

immune function. Methods: Data were abstracted from

the USIDNET Registry patients (n = 3,665) from 2003 to

2015. Site-specific cancer incidence rates were generated

for patients within the registry. Age adjusted incidence

rates for were generated using the SEER database for

comparison to the patients within the USIDNET registry.

Results: We observed a 1.34-fold excess relative risk of

cancer (p < .001) in patients with PIDD compared to age-

adjusted SEER population. In men we found excess relative

risk to increase to 1.8-fold excess relative risk of cancer (p

<.001), however in women the increase risk of cancer was

not significant. When analyzing the four most common

malignancies diagnosed in men and women in the United

States (lung, colon, breast, and prostate cancers) we found

no statistically significant increase in these diagnoses in

the USIDNET Registry patients. We observed statistically

significant increases in lymphoma in both men (10-fold

excess relative risk p < .001) and women (8-fold excess

relative risk p < .001) in the registry. In men within the

registry we observed a statistically significant increase in

skin cancer (4.45 fold excess relative risk p < .001) and

thyroid cancer (4-fold excess relative risk p = .002), and in

women we observed a statistically significant increase in

skin (3.19 fold excess relative risk p < .001) and stomach

cancer (3-fold excess relative risk p = .015).

Conclusions: Excess incidence of cancer occurred in

patients within the USIDNET Registry. This increased

incidence was principally driven by an excess of lymphoma

in specific PIDD populations, while no increased risk of the

most common solid tumor malignancies was observed.

These data point to a restricted role of the immune system

in protecting from specific cancers and question the role of

immunosurveillance in incident risk of common solid

tumor cancers.

ASCO 2016

48

Differences in Pulmonary Complications in Common

Variable Immunodeficiency and X-Linked

Agammaglobulinemia

Tamar Weinberger, MD, Paul Maglione, MD, and Charlotte

Cunningham-Rundles, MD

RATIONALE: Pulmonary disease is a leading cause of

morbidity and mortality in primary immunodeficiency, yet

factors underlying the development of this complication

are incompletely defined. Based upon differences in

immunoglobulin and lymphocyte levels, the incidence of

pulmonary complications may differ between those with

Common Variable Immunodeficiency (CVID) and X-Linked

Agammaglobulinemia (XLA), potentially exposing risk

factors for this complication.

METHODS: We analyzed the pulmonary complications and

laboratory characteristics of patients with CVID and XLA

entered in USIDNET.

RESULTS: 1107 patients with CVID and 314 with XLA born

between 1946 and 1996 were entered in USIDNET.

Incidence of interstitial lung disease (ILD, p = 0.0039) and

asthma (p = 0.0001) was significantly greater in CVID than

in XLA. There was no statistically significant difference in

bronchiectasis rates between the two groups (p= 0.2008).

Pneumonia rates between patients with CVID and XLA

were 58% and 65%, respectively (p= 0.0190). COPD rates

in CVID and XLA were 3% and 8%, respectively (p= 0.0002).

Patients with CVID had higher mean levels of IgG, IgA, and

IgM (p<0.001) and CD19 B cells (p=0.008) then patients

with XLA at initial diagnosis. Initial mean absolute

lymphocyte count and CD3 T cells were higher in patients

with XLA then with CVID (P<0.0001).

CONCLUSIONS: USIDNET patients with CVID are more

likely to be diagnosed with ILD and asthma, but less likely

to have COPD and pneumonia when compared to patients

with XLA. These observations are coupled with higher IgA,

IgM, and B cells, but lower T cells, in patients with CVID.

AAAAI Submission 2017

Clinical findings of patients with autonomic dominant

hyper IgE syndrome (HIES) in USIDNET

Yael Gernez1, Elizabeth Garabedian2, Angela Tsuang1,

Tukisa Smith1, Julien Mancini3 and Charlotte Cunningham-

Rundles1; 1Icahn School of Medicine at Mount Sinai, New

York, NY, 2NIH NHGRI, Medical Genetics Branch, Bethesda,

Maryland, 3Aix Marseille Univ, Marseille, France

RATIONALE: Autosomal dominant mutations in STAT3 lead

to HIES. Pneumonia with cavitation/abscess leading to

pneumatoceles and secondary fungal infections are major

causes of mortality and morbidity.

METHODS: We examined the clinical and biological

findings of patients with HIES entered in USIDNET, focusing

on patients with lung abscess.

RESULTS: 85 patients, born between 1950 and 2013 were

entered in USIDNET. 50 were female and 35 were male.

67.9% (53/78) were Caucasian, 12.8% (10/85) Hispanic or

African American and 6.4% (5/78) Asian. 54.2% (45/83)

had family history of HIES. Mean age at diagnosis of HIES

was 14 years (standard deviation: 13.9), mean IgE: 8,383.7

(standard deviation: 10,050). 72% (32/85) had skin

abscesses, 40% (34/85) retained teeth, 37.6% (32/85) had

fractures and 33% (28/85) had scoliosis. 49.4% (42/85) had

eosinophilia. 47.0% (40/85) were known to be on

trimethoprim-sulfamethoxazole, 16.4% (14/85) on

antifungal coverage, and 30.60% (26/85) on

immunoglobulin replacement therapy. Pneumonias were

attributed to Staphylococcus aureus (45.3%-24/53) or

Aspergillus fumigatus (26.4%-14/53). 18.8% (16/85) had a

history of lung abscess. Lung abscesses were associated

with drug reactions (p[Pearson]=0.01; OR: 4.03 [1.25-

12.97), also with significantly more depression (p[Fisher

exact test]=0.036 and lower Karnofsky index scores

(median [25th–75th percentiles]: 80 [70-90] versus 90 [80-

100], p [Mann-Whitney]=0.007).

CONCLUSIONS: Data from USIDNET provides a resource to

examine the characteristics of patients with these rare

diseases.

AAAAI Submission 2017

Broadening Our Understanding of the Noninfectious

Disease Complications of CVID Within the United States.

Jocelyn Farmer, MD, PhD, Department of Allergy &

Immunology, Massachusetts General Hospital, Boston,

MA, Mei-Sing Ong, PhD, Harvard Medical School, Boston,

MA, Lael Yonker, MD, Massachusetts General Hospital,

Boston, MA, Kathleen Sullivan, MD, PhD, Division of Allergy

and Immunology, Children's Hospital of Philadelphia,

Philadelphia, PA, Charlotte Cunningham-Rundles, MD, PhD,

Division of Clinical Immunology, Department of Medicine,

Icahn School of Medicine at Mount Sinai, New York, NY and

Jolan Walter, MD, PhD, Division of Allergy and

Immunology, University of South Florida, Tampa, FL

CVID epidemiology has been described almost exclusively

at large referral centers and centralized databases such as

the USIDNET. These data demonstrate the high morbidity

of noninfectious CVID sequelae. To establish the frequency

and severity of noninfectious sequelae at a large tertiary

49

care center, we conducted a retrospective cohort analysis

of patients with CVID diagnosed or treated at Partners

HealthCare Network Hospitals in Boston, MA (including

the Massachusetts General and Brigham and Women’s

Hospitals). Our cohort of 201 CVID patients was

comparable to the USIDNET with regard to native

immunoglobulin levels, B-cell immunophenotype, and

noninfectious disease complication rates. Using unbiased

clustering, we statistically differentiated the Partners

cohort into noninfectious disease sequelae endotypes

including atopic, lymphoproliferative, and auto-antibody-

mediated. Furthermore, we observed discrete

immunophenotypes (e.g. total and subclass

immunoglobulin levels, B-/T-cell subsets, and B-/T-cell

function) that were endotype-specific. These data

demonstrate the power of the USIDNET in validating

smaller cohort analyses and of unbiased statistical

approaches in elucidate novel or unexpected correlations

between immunophenoptype and divergent clinical

outcomes, which is of particular importance in the

heterogeneous CVID population.

CIS Submission 2017

Atopic Disease in Primary Immune Deficiency with B Cell

Dysfunction Amongst A USIDNET Cohort

Harmon G, DeFelice ML, Morsheimer M.

Division of Allergy & Immunology, Nemours A.I. duPont

Hospital for Children, Wilmington, DE, and Thomas

Jefferson University Hospital, Philadelphia, PA

RATIONALE: Atopic disease is an important consideration

in the care of patients with primary immune deficiencies

(PID), however, forming the diagnosis may be challenging

in patients with low or undetectable serum IgE. We aim to

describe the prevalence of allergic disease in a cohort of

patients with PID and B cell dysfunction, with the goal of

improving recognition of such patients who may benefit

from allergy treatment.

METHODS: A query was submitted to the USIDNET

database to examine associated conditions, allergic

reactions, and use of allergen immunotherapy in patients

with a diagnosis of a PID with B cell dysfunction.

RESULTS: The query identified 2391 cases, the majority

(63%) with a diagnosis of common variable

immunodeficiency disorders with unknown genetic basis

(CVID). Five patients were reportedly treated with

immunotherapy. For each PID within this cohort, allergic

rhinitis and asthma were reported in the following

percentages: Activated PI3Kd (0%, 0%),

agammaglobulinemia of unknown cause (10%, 20%), AID

deficiency (0%, 33%), BTK deficiency (2%, 9%), CD40L

deficiency (0%, 4%), CVID (5%, 29%), NEMO deficiency

(11%, 26%), Hyper IgM due to uncertain or unlisted cause

(<1%, 3%), hypogammaglobulinemia of unknown cause or

unlisted gene defect (<1%, 28%), isolated IgG subclass

deficiency (7%, 53%), selective IgA deficiency (6%, 45%),

specific antibody deficiency with normal IgG

concentrations and normal numbers of B cells (11%, 52%),

TACI deficiency (60%, 20%), transient

hypogammaglobulinemia of infancy with normal number

of B cells (11%, 33%).

CONCLUSIONS: This data suggests that atopic disease is

not uncommonly seen in the setting of B cell dysfunction.

CIS Submission 2017

50


USIDNET Repository

The goal of the cell repository which now housed at Coriell Institute is to establish a comprehensive catalog of genetic material from specific immune deficient patients. It’s open to interested investigators who may purchase materials. The repository has an inventory of 99 samples with 23 different PIDD’s. As of now, 98 samples have been requested and distributed to interested investigators.

Contact at Coriell Institute:

Abigail L. C. Amberson Project Associate Coriell Institute for Medical Research 403 Haddon Avenue, Camden, NJ 08103 856-966-5062 | [email protected] Table 1. USIDNET Repository Submissions

Sample Description Submitted

ATAXIA-TELANGIECTASIA; AT 6

BRUTON AGAMMAGLOBULINEMIA TYROSINE KINASE; BTK 8

CARTILAGE-HAIR HYPOPLASIA; CHH 5

CD40 LIGAND; CD40LG 1

CHRONIC GRANULOMATOUS DISEASE (XK-RELATED; CGD) - 306400 OR 314850 1

COMMON VARIABLE IMMUNODEFICIENCY 20

COMPLEMENT COMPONENT 2 DEFICIENCY 2

DIGEORGE SYNDROME; DGS 6

IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 1; HIGM1 5

IMMUNOGLOBULIN A DEFICIENCY 1; IGAD1 12

LEUKOCYTE ADHESION DEFICIENCY, TYPE I; LAD 1

LYMPHOPROLIFERATIVE SYNDROME, X-LINKED 4

NEUTROPENIA, TYPE UNKNOWN 2

OMENN SYNDROME 1

SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-NEGATIVE, DUE TO ADENOSINE DEAMINASE DEFICIENCY

2

SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-POSITIVE, NK CELL-NEGATIVE

1

SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED; SCIDX1 5

SH2 DOMAIN PROTEIN 1A; SH2D1A 1

SPECIFIC ANTIBODY DEFICIENCY WITH NORMAL IMMUNOGLOBULINS 6

SPECIFIC ANTIBODY DEFICIENCY WITH NORMAL IMMUNOGLOBULINS AND PEG-TEETH 2

THROMBOCYTOPENIA 1; THC1 1

WAS GENE; WAS 3

WISKOTT-ALDRICH SYNDROME; WAS 4

*Antibody deficiency with normal immunoglobulins and peg teeth; NEMO gene mutation has been excluded.

mailto:[email protected]

51

Table 2. Coriell Distribution in 2016

ID Date Reference Exp Lot Type Diagnosis Intent Type Intent Investigator Institution Country Source Cell Type

113460 1/5/2016 ID00078 0 CC OMENN SYNDROME

Functional Studies

To investigate genome editing in mutant cell lines.

CHATTERJEE

CITY OF HOPE

USA CC T-Lymphocyte

114576 3/25/2016 ID00018 0 CC IMMUNOGLOBULIN A DEFICIENCY1; IGAD1

Functional Studies

To see whether a particular microRNA has any role in selective IgA deficiency disease

MONOS CHILDREN'S HOSPITAL OF PHILADELPHIA

USA WB B-Lymphocyte


Functional Studies



USA WB B-Lymphocyte


Functional Studies



USA WB B-Lymphocyte


Functional Studies



USA WB B-Lymphocyte

119891 5/27/2016 ID00063 0 CC IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 1; HIGM1

Assay Development

used as a positive control in next generation DNA assay development

AYASS AYASS LUNG CLINIC PLLC

USA CC B-Lymphocyte

119891 5/27/2016 ID00064 A CC IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 1; HIGM1

Assay Development



USA CC B-Lymphocyte

119891 5/27/2016 ID00002 0 CC CD40 LIGAND; CD40LG

Assay Development



USA CC B-Lymphocyte

52



Functional Studies

To determine whether knocking down miR-6891-5p using antisense microRNA can restore IgA secretion in these cells.


JAPAN WB B-Lymphocyte


Functional Studies

To determine whether knocking down miR-6891-5p using antisense microRNA can restore IgA secretion in these cells.


USA WB B-Lymphocyte

121811 9/16/2016 ID00003 0 CC WAS GENE; WAS Functional Studies

The research aim is to protect WASp from degradation in WAS/XLT patients, restoring normal or near-normal protein levels and thus improving immune cell function. We will use smal molecule compounds that we have identified by screening compound libraries and test whehter they bind to WASp and stabilize the protein by protecting it from ubiquitylation and proteasomal degradation.

EREN XL THERAPEUTICS LTD

ISRAEL WB B-Lymphocyte

121811 9/16/2016 ID00004 A CC WAS GENE; WAS Functional Studies

Protect WASp from degradation in WAS/XLT patients, restoring normal or near-normal protein levels and improving immune cell function. Use smal molecule compounds that we have identified and test whehter they bind to WASp and stabilize the protein by protecting it from ubiquitylation and proteasomal degradation.

EREN XL THERAPEUTICS LTD

ISRAEL CC B-Lymphocyte

122171 10/7/2016 ID00016 0 CC DIGEORGE SYNDROME; DGS

Assay Development

To create artificial dried blood spots to use as positive controls to diagnose deletion 22q syndrome in neonates.

BULMAN CHILDREN'S HOSPITAL OF EASTERN ONTARIO

CANADA B-Lymphocyte

53


122984 11/30/2016

ID00001 0 CC BRUTON AGAMMAGLOBULINEMIA TYROSINE KINASE; BTK

Functional Studies

To study the interaction between B lymphocytes and fibroblast. To investigate the function of different BTK mutations in the specific cell lines.

KUO PHARMACYCLICS

USA B-Lymphocyte

122984 11/30/2016

ID00035 0 CC BRUTON AGAMMAGLOBULINEMIA TYROSINE KINASE; BTK

Functional Studies

To study the interaction between B lymphocytes and fibroblast. To investigate the function of different BTK mutations in the specific cell lines.

KUO PHARMACYCLICS

USA B-Lymphocyte

123058 11/30/2016

ID00003 1 DNA DYSKERATOSIS CONGENITA, X-LINKED; DKC

Control for Assay

These samples will be used as reference materials for the development and validation of a hereditary cancer assay.

XU TRUE HEALTH DIAGNOSTICS LLC

USA B-Lymphocyte

54

Table 3. Inventory of all USIDNET Repository Cells at Coriell

ID Sample Description Description # Left

126436 BRUTON AGAMMAGLOBULINEMIA TYROSINE KINASE; BTK B-Lymphocyte 19

189729 BRUTON AGAMMAGLOBULINEMIA TYROSINE KINASE; BTK B-Lymphocyte

126437 CD40 LIGAND; CD40LG B-Lymphocyte 22

126438 WAS GENE; WAS B-Lymphocyte 23

126439 WAS GENE; WAS B-Lymphocyte

126548 WAS GENE; WAS B-Lymphocyte 14

126440 SH2 DOMAIN PROTEIN 1A; SH2D1A B-Lymphocyte

126549 SH2 DOMAIN PROTEIN 1A; SH2D1A B-Lymphocyte 15

129508 COMMON VARIABLE IMMUNODEFICIENCY B-Lymphocyte 12




137940 DIGEORGE SYNDROME; DGS B-Lymphocyte 6

DIGEORGE SYNDROME; DGS B-Lymphocyte 2





138013

SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-NEGATIVE, DUE TO ADENOSINE DEAMINASE DEFICIENCY B-Lymphocyte 30

SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-NEGATIVE, DUE TO ADENOSINE DEAMINASE DEFICIENCY B-Lymphocyte 4

138067 IMMUNOGLOBULIN A DEFICIENCY 1; IGAD1 B-Lymphocyte 34

IMMUNOGLOBULIN A DEFICIENCY 1; IGAD1 B-Lymphocyte 4









BRUTON AGAMMAGLOBULINEMIA TYROSINE KINASE; BTK B-Lymphocyte 2


55



COMMON VARIABLE IMMUNODEFICIENCY B-Lymphocyte 2



138982 SPECIFIC ANTIBODY DEFICIENCY WITH NORMAL IMMUNOGLOBULINS AND PEG-TEETH B-Lymphocyte 15

SPECIFIC ANTIBODY DEFICIENCY WITH NORMAL IMMUNOGLOBULINS AND PEG-TEETH B-Lymphocyte 4






139207 COMMON VARIABLE IMMUNODEFICIENCY B-Lymphocyte

















141358 SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED; SCIDX1 B-Lymphocyte

SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED; SCIDX1 B-Lymphocyte 0

141359 LEUKOCYTE ADHESION DEFICIENCY, TYPE I; LAD B-Lymphocyte

LEUKOCYTE ADHESION DEFICIENCY, TYPE I; LAD B-Lymphocyte 0

141360 WISKOTT-ALDRICH SYNDROME; WAS B-Lymphocyte

WISKOTT-ALDRICH SYNDROME; WAS B-Lymphocyte 0

141361 ATAXIA-TELANGIECTASIA; AT B-Lymphocyte 13

56


ATAXIA-TELANGIECTASIA; AT B-Lymphocyte 0


ATAXIA-TELANGIECTASIA; AT B-Lymphocyte 0



141364 ATAXIA-TELANGIECTASIA; AT T-Lymphocyte

ATAXIA-TELANGIECTASIA; AT T-Lymphocyte 0

141365 ATAXIA-TELANGIECTASIA; AT B-Lymphocyte




141323 LYMPHOPROLIFERATIVE SYNDROME, X-LINKED B-Lymphocyte 13

LYMPHOPROLIFERATIVE SYNDROME, X-LINKED B-Lymphocyte 0

141367 LYMPHOPROLIFERATIVE SYNDROME, X-LINKED B-Lymphocyte 15

LYMPHOPROLIFERATIVE SYNDROME, X-LINKED B-Lymphocyte 0

141368 SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED; SCIDX1 B-Lymphocyte 11


141369 IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 1; HIGM1 B-Lymphocyte 16

IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 1; HIGM1 B-Lymphocyte 0


IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 1; HIGM1 B-Lymphocyte 0

141324 CHRONIC GRANULOMATOUS DISEASE (XK-RELATED; CGD) - 306400 OR 314850 B-Lymphocyte 16

CHRONIC GRANULOMATOUS DISEASE (XK-RELATED; CGD) - 306400 OR 314850 B-Lymphocyte 0







152962 SPECIFIC ANTIBODY DEFICIENCY WITH NORMAL IMMUNOGLOBULINS B-Lymphocyte 15

SPECIFIC ANTIBODY DEFICIENCY WITH NORMAL IMMUNOGLOBULINS B-Lymphocyte 4




57



NEUTROPENIA, TYPE UNKNOWN B-Lymphocyte 2

155150 NEUTROPENIA, TYPE UNKNOWN B-Lymphocyte 7

155955 NEUTROPENIA, TYPE UNKNOWN B-Lymphocyte 8





170750 IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 1; HIGM1 B-Lymphocyte

177974 COMPLEMENT COMPONENT 2 DEFICIENCY B-Lymphocyte 1

177975 COMPLEMENT COMPONENT 2 DEFICIENCY B-Lymphocyte 1

THROMBOCYTOPENIA 1; THC1 B-Lymphocyte 1


177975 SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-POSITIVE, NK CELL-NEGATIVE B-Lymphocyte 1

178644 OMENN SYNDROME T-Lymphocyte 13

178645 CARTILAGE-HAIR HYPOPLASIA; CHH T-Lymphocyte 14




178651 CARTILAGE-HAIR HYPOPLASIA; CHH B-Lymphocyte 12

178835 SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED; SCIDX1 B-Lymphocyte 14

178836 HYPERIMMUNOGLOBULIN E RECURRENT INFECTION SYNDROME, AUTOSOMAL DOMINANT B-Lymphocyte 15

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2016 USIDNET Industry and Other Support

The following is a summary of the industry support requests, and outcomes for 2016:

Awarded grant in 2011 for $28,000 for patient enrollment costs. Received $21,000 sinceagreement signed and remaining $7,000 will receive early 2012.

Resubmitted for an additional $32,250 support for 2012 on December 21, 2011o Outcome: We did not receive requested funding

Applied for a Research Fellowship grant in December 2013 for the purpose of activatingUSIDNET registry data to produce publications and/or launch future studies.

o Awarded $20,000 from Baxter in 2014.

Applied for renewal of the Research Fellowship grant in December 2015o Grant was renewed for $20,000 in 2016.

Applied for a Research Fellowship grant in July of 2016 for the purpose of activating USIDNETregistry data to study lung disease in PIDD

o Awarded $10,000 from ADMA Biologics in 2016o Proposal submissions for the fellowship funds are under review in December 2016

Shire

ADMA Biologics

http://www.talecris.com/talecris-biotherapeutics-home.htm


59

Resubmitted proposal on April 7, 2011 to enroll patients with ADA-SCID to define outcomes,compare degree of immune reconstitution, and define treatment variables.

The Sigma Tau agreement to fund an ADA SCID Sub-registry was fully executed on September25, 2012.

The total budget for the USIDNET ADA SCID Sub- registry is $51,000.

The first payment of $31,600 was used to cover the cost of ADA SCID sub-Registry computerprogramming (total cost) and stipends for 25 charts.

The final payment was distributed to USIDNET from Sigma Tau in 2014.

Received $75,000 for educational and mentoring programs in 2010 from TalecrisBiotherapeutics that was acquired by Grifols.

Resubmitted for an additional $75,000 support for 2012 on December 7, 2011o Requested $25,000 of the $75,000 to redesign the USIDNET website in 2012 (one time

request)o Requested $50,000 of the $75,000 to support educational and mentoring programs

Outcome: We did not receive requested funding

Working on a grant application to CSL Behring for the purpose of a research fellowship (Inprogress).

Received $32,350 in December 2010 for patient enrollment costs, Registry upgrades and

mandated IIRB reviews

Resubmitted for an additional $32,350 support for 2012 on November 7, 2011

o Outcome: We did not receive requested funding

Sigma-Tau Pharmaceuticals

Grifols

CSL Berhing



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