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Published in: Journal of Gastroenterology 8/2023

Open Access 13-06-2023 | Primary Sclerosing Cholangitis | Original Article―Liver, Pancreas, and Biliary Tract

Anti-integrin αvβ6 autoantibodies in patients with primary sclerosing cholangitis

Authors: Hiroyuki Yoshida, Masahiro Shiokawa, Takeshi Kuwada, Yuya Muramoto, Sakiko Ota, Yoshihiro Nishikawa, Hirona Maeda, Nobuyuki Kakiuchi, Kanako Okamoto, Hajime Yamazaki, Masataka Yokode, Takeharu Nakamura, Shimpei Matsumoto, Tomonori Hirano, Hirokazu Okada, Saiko Marui, Yuko Sogabe, Tomoaki Matsumori, Atsushi Mima, Norimitsu Uza, Yuji Eso, Atsushi Takai, Ken Takahashi, Yoshihide Ueda, Yuzo Kodama, Tsutomu Chiba, Hiroshi Seno

Published in: Journal of Gastroenterology | Issue 8/2023

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Abstract

Background

Patients with primary sclerosing cholangitis (PSC) possess autoantibodies against biliary epithelial cells. However, the target molecules remain unknown.

Methods

The sera of patients with PSC and controls were subjected to enzyme-linked immunosorbent assays to detect autoantibodies using recombinant integrin proteins. Integrin αvβ6 expression in the bile duct tissues was examined using immunofluorescence. The blocking activity of the autoantibodies was examined using solid-phase binding assays.

Results

Anti-integrin αvβ6 antibodies were detected in 49/55 (89.1%) patients with PSC and 5/150 (3.3%) controls (P < 0.001), with a sensitivity and specificity of 89.1% and 96.7%, respectively, for PSC diagnosis. When focusing on the presence or absence of IBD, the proportion of the positive antibodies in PSC with IBD was 97.2% (35/36) and that in PSC alone was 73.7% (14/19) (P = 0.008). Integrin αvβ6 was expressed in bile duct epithelial cells. Immunoglobulin (Ig)G from 15/33 patients with PSC blocked integrin αvβ6-fibronectin binding through an RGD (Arg–Gly–Asp) tripeptide motif.

Conclusions

Autoantibodies against integrin αvβ6 were detected in most patients with PSC; anti-integrin αvβ6 antibody may serve as a potential diagnostic biomarker for PSC.
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Metadata
Title
Anti-integrin αvβ6 autoantibodies in patients with primary sclerosing cholangitis
Authors
Hiroyuki Yoshida
Masahiro Shiokawa
Takeshi Kuwada
Yuya Muramoto
Sakiko Ota
Yoshihiro Nishikawa
Hirona Maeda
Nobuyuki Kakiuchi
Kanako Okamoto
Hajime Yamazaki
Masataka Yokode
Takeharu Nakamura
Shimpei Matsumoto
Tomonori Hirano
Hirokazu Okada
Saiko Marui
Yuko Sogabe
Tomoaki Matsumori
Atsushi Mima
Norimitsu Uza
Yuji Eso
Atsushi Takai
Ken Takahashi
Yoshihide Ueda
Yuzo Kodama
Tsutomu Chiba
Hiroshi Seno
Publication date
13-06-2023
Publisher
Springer Nature Singapore
Published in
Journal of Gastroenterology / Issue 8/2023
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-023-02006-6

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