April 2000

692

SERUM BETA·CROSSLAPS CONCENTRATION AND ITS COR·RELATION TO THE BONE MINERAL DENSITY OF PATIENTSWITH INFLAMMATORY BOWEL DISEASE.Pal Miheller, Karoly Racz, Miklos Toth, Annamaria Nemeth, Edit Molnar,Attila Bezzegh, Herszenyi Laszlo, Zsolt Tulassay, 2nd Dept of Int Med,Semmelweis Univ of Medicine, Budapest, Hungary; 2nd Dept Int Med,Semmelweis Univ of Medicine , Budapest, Hungary.

Background: Patients with inflammatory bowel disease (IBD) have de­creased bone mineral density (BMD). According to the reported data, themetabolic bone disorder of patients with Crohn's disease (CD) is moresevere than that of patients with ulcerative colitis (UC). Beta-CrossLaps isa C-telopeptide breakdown product of type 1 collagen, reflecting the boneresorption. Aims: The aim of the present study was to determine theclinical relevance of serum beta-CrossLaps (bCL) measurement in patientswith inflammatory bowel diseases (IBD). Patients and methods: 50 IBDpatients (27 UC, 23 CD) and 45 healthy controls (HC) were studied. Themale/female ratio was 28/22 in the IBD group, and 12133 in the HC group.The mean age in IBD and HC groups were 37.5 and 31.5 years, resp. Bonemineral density of the lumbar spine. femoral neck and the distal third ofradius was measured by DEXA method (Hologic QDR 4500C). SerumbCL was determined by immunoassay (Elecsys, Roche). Results: SerumbCL levels of healthy subjects (0.276~0.146: meanz Sfr) were within thereference range provided by the manufacturer (0-0.35 ng/ml). The differ­ence in bCL concentration between the CD and HC groups was significant(0.425~0.27 vs. 0.276~ 0.146; p=0.007), while the bCL levels ofUC andHC groups was not different (0.278~0.208 vs. 0.276 ~0.146). Serum bCLlevels and the lumbar spine BMD z-scores corraleted significantly inpatients with CD (r= - 0.51, p=0.019). There were no significant corre­lations between the serum bCL and z-scores at the femoral neck and thedistal third of radius in patients with CD and UC, resp. Conclusion: Thereis a significant correlation between serum bCL concentration and the bonemineral density of CD patients. Serum bCL level correlates to the bonemineral density of the lumbar spine (z-score). Serum bCL measurementmay be a useful laboratory marker for the assessment of the metabolic bonedisease in patients with lBO, particularly in those with CD.

693

DIAGNOSTIC MISCLASSIFICATION OF PATIENTS WITH PRE­SUMED INFLAMMATORY BOWEL DISEASE (IBD),David N. Moskovitz, Mark S. Silverberg, Robin S. Mcleod, Gordon R.Greenberg, Zane Cohen, Katherine A. Siminovitch, A. Hillary Steinhart ,Mount Sinai Hosp, Toronto, ON, Canada.

Aim: The diagnosis of IBD based on clinical, histologic, radiologic andendoscopic criteria, may sometimes be difficult and errors can occur. Thisstudy describes the rate and type of misclassification in a large populationof individuals referred to participate in an IBD genetics study. Methods:The records of 1096 patients who were entered into the IBD GeneticsStudy were reviewed by one author using standardized diagnostic criteria .In all cases the original diagnosis and the updated diagnosis were docu­mented and the reasons for the change in diagnosis were reported. Patientswere grouped according to type of diagnostic change: (l) diagnosischanged from Crohn's disease (CD) to ulcerative colitis (UC) or from UCto CD; (2) change from UC or CD to indeterminate colitis (IC); (3) changefrom UC or CD to no diagnosis of IBD; (4) change from IC to UC or CD;(5) change from IC to no diagnosis of IBD. Results: Sixty-eight of 1096(6.2%) individuals had a change in diagnosis from that originally reported.Reasons for change in diagnosis were divided into 4 categories: (R I)discordance between the clinical history, endoscopic, or pathological re­sults; (R2) disease pattern changed over time; (R3) diagnosis remained thesame and no change in diagnosis should have been documented ; (R4)insufficient information was available to confirm either the original diag­nosis, the current diagnosis, or both. The distribution of reasons for changeby type of change are listed in the table below. Conclusions: Of patientsreferred to an IBD genetics study 6.2% had a change made to their originaldiagnosis, most commonly from CD or UC to no diagnosis of IBD.Reasons for these changes were usually discordance between the clinicalhistory, endoscopic. or pathological results, and changing disease patternover time. These results have important implications for clinical andgenetic studies involving IBD patients and suggest that careful documen­tation of diagnosis is required.

AGAAI05

694

IGG AND IGA ANTI-SACCHAROMYCES CEREVISIAE ANTIBOD·IES (ASCA) DETEcnON BY ELISA IN CROHN'S DISEASE, UL·CERATIVE COLITIS AND HEALTHY PATIENT GROUPS.Gary L. Norman, Zakera Gandhi, Tiffany M. Crowther, Walter Binder,Verena Kratzer, Walter Reinisch, Harold Vogelsang, Harold VogelsangINDVA Diagnostics. San Diego, CA; Gen Hosp of Vienna. Univ Vienna,Vienna, Austria.

IgG and IgA antibodies directed against mannose sequences in the cell wallof S.cerevisiae are significantly more prevalent in patients with Crohn' sdisease (CD) than in patients with ulcerative colitis (UC)or in normalhealthy controls. In the present study, we evaluated the INOVA QuantaLitefM IgG and IgA ASCA ELISA kits on 297 healthy normal individualsand a panel of 39 known and 187 blinded specimens from clinically­defined patients assembled at the Univ. of Vienna. The specificity of theIgG and IgA ASCA ELISA kits on the healthy controls was 94.9%(2781293) and 98.0% (289/295) respectively. Results on the clinical panelconfirmed the high prevalence of ASCA in CD patients (74% IgG+ , 43%IgA+ )compared to UC (15% IgG+ , 0% IgA+ )or healthy controls(2%IgG+. 2% IgA+ )(see Table I). It is notable that all 46 specimens with bothpositive ASCA IgG and IgA results were CD specimens and none (01104)of the UC or healthy controls were both IgG and IgA positive. TheASCA reactivities in CD patients varied from low to very high. Specimenswith high IgGllow IgA ASCA values and specimens with high IgAllowIgG ASCA values were observed. The clinical significance of these obser­vations is unclear and is an area of future studies. Our study confirms thata high percent of CD patients have ASCA, in contrast to UC or controlpatients. The assays were 100% specific for CD when specimens were bothIgG and IgA ASCA positive . Availability of standardized and reproducibleIgG and IgA ASCA ELISA tests may provide a valuable noninvas ive aidfor clinicians evaluating and classifying patients with symptoms of inflam­matory bowel disease.

QuantaLite"" IgGand IgAELISA ResultsonPatient Panels

Diagnosis n = '10 IgGpos. %IgApos %IgGand IgApos.

Specificity panel: 297 5.1 (151293) 20(61295) 0(01295)Clinical panel:Crohn dis. 115 73.9(82111 1) 42.7 (47/110) 41 .8(461110)Ulcerative colitis 63 150(9/59) 0(0/61) 0(0/59)Healthy controls 48 2.2 (1 /45) 2.1(1147) 0(0/45)

NOTE: equivocal resultswere excluded from calculations

695

DIAGNOSTIC VALUE OF ASCA (ANTI-SACCHAROMYCESCEREVISIAE ANTmODIES) AND PANCA (PERINUCLEAR AN·TINEUTROPHIL CYTOPLASMIC ANTmODIES) IN INFLAMMA·TORY BOWEL DISEASE.Marc Peeters, Severine Vermeire, Sofie Joossens, Fred Monsuur, XavierBossuyt, Paul Rutgeerts, Univ hospitals Gasthuisberg, Leuven, Belgium.

Introduction and Aims:Accurate serological markers are desirable for thediagnosis of inflammatory bowel disease (IBD), especially for differenti­ating Crohn's disease (CD) from ulcerative colitis (DC). These markerswould be of extreme value in cases of indeterminate colitis (lC) whereexact diagnosis can not be made with conventional criteria. We previouslyshowed that pANCA is associated with UC in 57% and ASCA with CD in62% of the patients in our population, However.the value of these markersin screening for IBD is still an open question. Therefore , we investigatedsensitivity, specificity and predictive value of pANCA and ASCA within aBelgian IBD population. a group of non-IBD diarrheal illnesses andhealthy controls. Methods :ASCA and pANCA were studied in a largecohort of consecutive IBD patients (n= 582: 407 CD. 147 DC and 28 IC),non-IBD diarrheal illnesses (n= 63) and healthy controls (n= 118). Anindirect immunofluorescence technique and a standardised ELISA wereperformed for detection of pANCA and ASCA, respectively. The ASCAassay was obtained from Dr 0 Poulain (Lille, France). Results:(see table)Conclusion: Although the sensitivity of ASCA and pANCA respectively islow, their specificity is high, especially when combining both markers.Therefore , the combination of ASCA and pANCA should be used in IBDdiagnosis.

Table1 : Diagnosticaccuracy of theserological tests todistinguishbetween CD. UCand non-ISDRl 6(46%) 5(29%) 11(41%) 4R2 5(38%) 4(24%) 4(1 5%) 1 sensitivity specificity PPV NPVR3 1(8%) 4[24%) 3(11%) 1R4 1(8%) 4(24%) 9(33%) 1 ASCA+ 60% 90% 88% 65%

pANCA+ 50% 95% 70% 88%ASCA+/pANCA· 56% 94% 92% 63%pANCA+/ASCA· 44% 98% 89% 87%