Mo1698 Clinical, Genetic and Serological Markers of Disease Behaviour in Colonic Inflammatory Bowel Disease

Abstract

Background/Aim: Colonic IBD is defined by colon-only involvement of Crohn's disease (CD), ulcerative colitis (UC) or IBDU (Montreal Classification). There is evidence that these entities are clinically and genetically similar. It would be of clinical value to determine who is at risk of complications of colonic IBD such as strictures or penetrating complications. This study aimed to identify factors associated with small and large bowel stricturing or penetrating outcomes in IBD confined to the colon. Methods: We identified UC, IBDU and colon-only CD patients at Mount Sinai Hospital in Toronto with ≥5 years of documented follow-up and with serum and DNA available. We evaluated variables that may distinguish subjects with a Crohn's-like outcome versus those with a UC-like outcome. A Crohn's-like outcome was defined as new-onset of colonic or small bowel B2 or B3 behaviour. A UC-like outcome was defined as those subjects with inflammatory behaviour confined to the colon during the study follow up. Factors assessed included: demographic variables, CD-associated features on histology or endoscopy, 9 SNPs that were previously found to be CDand UC-specific (3 within NOD2, 3 from ATG16L1 and IRGM, 1 in HLA-DRA and 2 in gene deserts on 1p36 and 5q31), and ASCA IgG and IgA, anti-Cbir1, anti-OmpC and pANCA seroprevalence. Pearson's χ2 test was used to compare proportions; Wilcoxon rank-sum test was used to compare continuous variables. Logistic regressionmodels were applied for genetic association analysis using an additive genetic model; Odds ratios (OR) and 95% confidence intervals were estimated. Results: 620 patients with colonic IBD (86% Caucasians, 51.8% females, median age at diagnosis =26) were reviewed (164 CD, 39 IBDU and 417 UC). Serological and genetic data were available in 378 and 515 subjects, respectively. CD-like behaviour occurred in 82 (13.2%) patients. Smoking at diagnosis, Caucasian ethnicity and a positive family history of CD were not associated with CD-like outcomes. Conversely, being seropositive for ASCA IgG and IgA and anti-Cbir1 was associated with CD-like behaviour (OR=2.32 p=0.02, OR=5.26 p<0.0001; OR=2.17 p=0.01, respectively) and being positive for pANCA was protective (OR=0.28, p=0.0002). Clinical subtyping of CD (OR=3.91, p<0.00001), CDfeatures at the first pathology report (OR=3.31, p=0.0006) and a history of perianal disease (OR=5.02, p<0.0001) were highly predictive of CD-like outcomes. None of the SNPs investigated were associated with CD-like outcomes. Conclusions: In this large cohort of colonic IBD, the presence of ASCA and anti-Cbir1 were strongly associated with CD-like disease behaviour and pANCA was protective. The 9 SNPs investigated were not associated with CD-like behaviour suggesting that these specific SNPs may not be of value in the identification of individuals at risk of disease complications.