Integrin αVß6 - autoantigen and driver of epithelial remodeling in colon and bile ducts in primary sclerosing cholangitis and inflammatory bowel disease.
Dominik Roth, Miriam M Düll, Ludwig J Horst, Aylin Lindemann, Xenia Malzer, Kristina Koop, Sebastian Zundler, Marcel Vetter, André Jefremow, Raja Atreya, Carol Geppert, Sören Weidemann, Maximilian J Waldner, Peter Dietrich, Claudia Günther, Luis E Munoz, Martin Herrmann, Alexander Scheffold, Markus F Neurath, Jürgen Siebler, Christoph Schramm, Andreas E Kremer, Moritz Leppkes
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引用次数: 0
Abstract
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.