Integrin αVβ6: Autoantigen and Driver of Epithelial Remodeling in Colon and Bile Ducts in Primary Sclerosing Cholangitis and Inflammatory Bowel Disease.

Roth D, Düll M, Horst LJ, Lindemann A, Malzer X, Koop K, Zundler S, Vetter M, Jefremow A, Atreya R, Geppert CI, Weidemann S, Waldner M, Dietrich P, Günther C, Munoz LE, Herrmann M, Scheffold A, Neurath M, Siebler J, Schramm C, Kremer A, Leppkes M (2025)

Publication Language: English

Publication Type: Journal article

Publication year: 2025

Journal

Journal of Crohns & Colitis Elsevier

Book Volume: 19

Article Number: jjae131

Journal Issue: 2

DOI: 10.1093/ecco-jcc/jjae131

Abstract

BACKGROUND: Recently, autoantibodies directed against the epithelial adhesion protein integrin αVβ6 have been identified that are strongly associated 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. METHODS: We detected anti-αVβ6 by an enzyme-linked immunosorbent assay in sera collected at 2 German tertiary centers, including healthy controls (N = 62), UC (N = 36), Crohn's disease (CD, N = 65), PSC-inflammatory bowel diseases (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). In addition, 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. CONCLUSIONS: Anti-αVβ6 frequently occurs in patients suffering from PSC, especially in PSC-IBD. Anti-αVβ6 levels positively correlate to IBD activity in PSC-IBD, but may also occur in the absence of clinically manifest IBD in PSC.

Authors with CRIS profile

Dominik Roth Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Miriam Düll Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Aylin Lindemann Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Xenia Elsner Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Kristina Koop Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Sebastian Zundler Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Marcel Vetter Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology André Jefremow Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Raja Atreya Professur für Translationale Immunforschung bei chronisch entzündlichen Darmerkrankungen Carol-Immanuel Geppert Institute of Pathology Maximilian Waldner Professur für Funktionelle Bildgebung in der Medizin Peter Dietrich Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Claudia Günther Professur für Gastrointestinale Pathophysiologie Luis Munoz Becerra Department of Medicine 3 – Rheumatology and Immunology Martin Herrmann Department of Medicine 3 – Rheumatology and Immunology Markus Neurath Lehrstuhl für Innere Medizin I (Medizin 1) Jürgen Siebler Professur für Hepatologie Andreas Kremer Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Moritz Leppkes Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology

Related research project(s)

Interfaces in Immunomedicine (iIMMUNE) (iIMMUNE_ACS) May 1, 2022 - April 30, 2027 D040: The role of the DEAD-box RNA helicase DDX46 in liver cancer March 1, 2023 - Feb. 28, 2026 J099: The role of reactive carbonyls in metabolic-dysfunction associated neuropathic pain and chronic liver disease Oct. 1, 2022 - Sept. 30, 2025

Involved external institutions

Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE)

How to cite

APA:

Roth, D., Düll, M., Horst, L.J., Lindemann, A., Malzer, X., Koop, K.,... Leppkes, M. (2025). Integrin αVβ6: Autoantigen and Driver of Epithelial Remodeling in Colon and Bile Ducts in Primary Sclerosing Cholangitis and Inflammatory Bowel Disease. Journal of Crohns & Colitis, 19(2). https://doi.org/10.1093/ecco-jcc/jjae131

MLA:

Roth, Dominik, et al. "Integrin αVβ6: Autoantigen and Driver of Epithelial Remodeling in Colon and Bile Ducts in Primary Sclerosing Cholangitis and Inflammatory Bowel Disease." Journal of Crohns & Colitis 19.2 (2025).

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