Integrin αVß6 - autoantigen and driver of epithelial remodeling in colon and bile ducts in primary sclerosing cholangitis and inflammatory bowel disease

OBJECTIVE Recently, autoantibodies directed against the epithelial adhesion protein integrin αVβ6 have been identified which strongly associate with ulcerative colitis (UC). We aimed to elucidate whether anti-integrin αVβ6 (anti- αVβ6) is present in primary sclerosing cholangitis (PSC), its associated inflammatory bowel disease or other cholestatic liver diseases and their persistence after proctocolectomy. DESIGN We detected anti- αVβ6 by an enzyme-linked immunosorbent assay in sera collected at two German tertiary centers, including healthy controls (N=62), UC (N=36), Crohn's disease (CD, N=65), PSC-IBD (78 samples from N=41 patients), PSC without IBD (PSC, 41 samples from N=18 patients), primary biliary cholangitis (PBC, N=24), autoimmune hepatitis (AIH, N=32), secondary sclerosing cholangitis (SSC, N=12) and metabolic dysfunction-associated steatotic liver disease (MASLD, N=24). Additionally, sera after proctocolectomy were studied (44 samples / N= 10 patients). Immunofluorescent analyses were performed in tissue samples from liver, large bile duct from surgical resections and colon of PSC patients. RESULTS Anti- αVβ6 occurred in 91% of UC, 17% of CD, 73% of PSC-IBD, 39% of PSC, 4% of PBC, 14% of AIH, and 0% of healthy controls, SSC or MASLD. Integrin αVβ6 is selectively expressed in disease-associated epithelia of both bile duct and colon. Anti- αVβ6 levels correlate moderately with intestinal disease activity in PSC-IBD, but only weakly with biliary disease. CONCLUSION Anti- αVβ6 frequently occur in patients suffering from PSC, especially in PSC-IBD. Anti- αVß6 levels positively correlate to IBD activity in PSC-IBD, but may also occur in the absence of clinically manifest IBD in PSC.