OP13 Anti-integrin αvβ6 autoantibodies are increased in PSC-IBD and correlate with liver disease severity

Abstract

Abstract Background Anti-integrin αvβ6 autoantibodies (anti-αvβ6) are a novel biomarker of ulcerative colitis (UC) that precede disease diagnosis by up to 10 years. Given that integrin αvβ6 is also expressed on the biliary epithelium and that primary sclerosing cholangitis (PSC) co-occurs with inflammatory bowel disease (IBD) in up to 90% of patients, we aimed to determine the prevalence of anti-αvβ6 in patients with PSC and to understand the impact of anti-αvβ6 on PSC disease course. Methods Three cohorts of pre-liver transplant patients with PSC and controls (IBD and non-IBD) were recruited from New York, Lisbon and Miami. Anti-αvβ6 levels were measured using ELISA and normalized for serum IgG concentration. Statistical analyses across groups and clinical parameters were performed using the Kruskal-Wallis and Spearman correlation test. Multivariable linear regression was conducted to assess the association between anti-αvβ6 and liver disease severity, correcting for covariates. A mixed-effects model was applied to assess change in anti-αvβ6 over time. Results In total, 94 patients with PSC (53 (56.4%) PSC-UC, 20 (21.3%) PSC-Crohn’s disease (CD) and 21 (22.3%) PSC alone) and 129 controls (74 (57.4%) IBD and 55 (42.6%) non-IBD) were enrolled; table 1 shows the baseline characteristics of the patients with PSC. Follow-up samples (n=22) were collected from 1 up to 3 years after initial baseline sampling from 17 PSC patients. Median (IQR) age was similar in PSC patients (43, 33-56 years) and controls (47, 32-62 years; p=0.59). Median (IQR) anti-αvβ6 levels were significantly higher in PSC-UC (1.07, 0.48-2.65) and UC (1.83, 1.12-3.03) compared to PSC alone (0.40, 0.23-0.63; p=0.0004 and p<0.0001 respectively) and non-IBD controls (0.39, 0.17-0.65; p<0.0001 and p<0.0001 respectively). Anti-αvβ6 levels were comparable between PSC alone and non-IBD controls (p>0.999) (figure 1A). Anti-αvβ6 levels did not increase over time (p=0.23). A positive correlation between anti-αvβ6 levels and the Mayo PSC risk score (r=0.28, p=0.008) as well as alkaline phosphatase (r=0.29, p=0.007) was observed (figure 1B). These associations remain significant after correcting for covariates including age at diagnosis of PSC, gender, race/ethnicity and IBD type in a multivariable linear regression. Conclusion Anti-αvβ6 autoantibodies are a new biomarker of PSC-IBD and are associated with liver disease severity.