P0560 Levels of disease-associated anti-integrin αVβ6 are substantially reduced after proctocolectomy in ulcerative colitis but persist in primary sclerosing cholangitis

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Abstract Background Recently, autoantibodies directed against the epithelial adhesion protein integrin αVβ6 have been identified that strongly associate with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC) with potential disease-driving effects. The presence of anti-αVβ6 in PSC without IBD is under debate. Moreover, data on the effect of proctocolectomy on autoantibody levels remains scarce. Methods Anti-αVβ6-directed autoantibodies were detected by a commercial enzyme-linked immunosorbent assay in patient sera, including healthy controls (N = 62), ulcerative colitis (N = 36), Crohn’s disease (CD, N = 65), PSC with concomitant IBD (78 samples from N = 41 patients), PSC without clinically manifest IBD (41 samples from N = 18 patients). Additionally, sera after proctocolectomy were studied (44 samples / N= 10 patients: 5 with UC, 5 with PSC). Immunofluorescent analyses of the target autoantigen were performed in liver, large bile ducts from surgical resections and colon tissue samples of PSC patients and single-cell RNA seq datasets were studied. Results The target autoantigen is expressed in disease-associated epithelia in the colon, in cholangiocytes in fibrotic portal fields and periductular glands of the large bile ducts as detected in immunofluorescence and single-cell RNA sequencing datasets. Anti-αVβ6 antibodies occur in 74% of patients with PSC with IBD, but also in 39% of patients with PSC without manifest IBD with lower levels. Anti-αVβ6 levels correlate with intestinal disease activity in patients with primary sclerosing cholangitis. Interestingly, proctocolectomy reduces autoantibody levels more strongly in UC than in PSC patients. Conclusion Disease-associated anti-integrin αVβ6 autoantibodies are also present in PSC without IBD with lower levels, assay sensitivity being a crucial determinant of detection. Moreover, proctocolectomy more strongly reduced autoantibody levels in UC than in PSC. Preferential autoantibody persistence in PSC after proctocolectomy might explain the increased incidence of chronic pouchitis in PSC.

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