Anti-integrin αvβ6 Autoantibodies Are Increased in Primary Sclerosing Cholangitis Patients With Concomitant Inflammatory Bowel Disease and Correlate With Liver Disease Severity

Background & Aims: Anti-integrin αvβ6 autoantibodies (anti-αvβ6) are found in more than 50% of individuals with ulcerative colitis (UC). We aimed to determine the prevalence of anti-αvβ6 in patients with primary sclerosing cholangitis (PSC) and their association with liver disease severity. Methods: Four cohorts of pre-liver transplant patients with PSC were recruited. Patients with inflammatory bowel disease (IBD) and healthy controls (HCs) served as comparators. Total IgG and anti-αvβ6 levels were measured using enzyme-linked immunosorbent assay. Olink inflammation panel was run on a subset of samples. Multivariable linear regression analysis was performed to assess the association between anti-αvβ6 and indices of liver disease severity. Results: A total of 137 patients with PSC (including 76 with PSC-UC, 33 with PSC-Crohn's disease (CD), and 28 with PSC alone) and 160 controls (including 91 with IBD and 69 HCs) were enrolled. Anti-αvβ6 levels were significantly higher in PSC-UC and PSC-CD compared with PSC alone (P < .0001 and P < .003) and HCs (P < .0001 and P < .0001). However, anti-αvβ6 levels in PSC alone were not increased compared with HCs. In patients with PSC-IBD, anti-αvβ6 levels correlated with markers of liver disease severity, including alkaline phosphatase level (r = 0.32; P = .004), the revised Mayo PSC risk score (r = 0.25; P = .02), and liver stiffness measurement (r = 0.43; P = .008) after adjusting for age, gender, race/ethnicity, and IBD subtype. Additionally, anti-αvβ6 levels were associated with markers of systemic inflammation and tissue remodeling. Conclusion: Anti-αvβ6 autoantibodies identify a subset of patients with PSC with concomitant IBD.