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ResearchIn-Press PreviewGastroenterology Open Access | 10.1172/jci.insight.192953

Characteristics of anti-integrin αvβ6 autoantibodies in patients with ulcerative colitis

Masahiro Shiokawa,1 Yoshihiro Nishikawa,1 Ikuhisa Takimoto,1 Takeshi Kuwada,1 Sakiko Ota,1 Darryl Joy C. Juntila,1 Takafumi Yanaidani,1 Kenji Sawada,1 Ayako Hirata,1 Muneji Yasuda,1 Koki Chikugo,1 Risa Nakanishi,1 Masataka Yokode,1 Yuya Muramoto,1 Shimpei Matsumoto,1 Tomoaki Matsumori,1 Tsutomu Chiba,1 and Hiroshi Seno1

1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

2Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Philippines

3Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Osaka, Japan

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1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

2Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Philippines

3Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Osaka, Japan

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1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

2Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Philippines

3Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Osaka, Japan

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1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

2Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Philippines

3Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Osaka, Japan

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1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

2Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Philippines

3Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Osaka, Japan

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1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

2Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Philippines

3Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Osaka, Japan

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1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

2Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Philippines

3Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Osaka, Japan

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1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

2Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Philippines

3Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Osaka, Japan

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1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

2Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Philippines

3Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Osaka, Japan

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1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

2Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Philippines

3Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Osaka, Japan

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1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

2Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Philippines

3Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Osaka, Japan

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1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

2Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Philippines

3Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Osaka, Japan

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1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

2Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Philippines

3Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Osaka, Japan

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1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

2Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Philippines

3Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Osaka, Japan

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1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

2Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Philippines

3Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Osaka, Japan

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1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

2Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Philippines

3Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Osaka, Japan

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1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

2Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Philippines

3Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Osaka, Japan

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1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

2Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Philippines

3Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Osaka, Japan

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Published January 8, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.192953.
Copyright © 2026, Shiokawa et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published January 8, 2026 - Version history
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Abstract

Ulcerative colitis (UC) is a chronic inflammatory condition of the colon that primarily affects the mucosal layer. Previously, we identified autoantibodies against integrin αvβ6 in patients with UC. In this study, we established monoclonal antibodies (mAbs) from patients with UC to reveal the features and functions of these anti-integrin αvβ6 autoantibodies. We identified two shared heavy chain complementarity-determining region (CDR) 3 amino acid sequences among different patients with UC. Notably, several mAbs contained the RGD sequence in their heavy chain CDR3 that mimicked the key recognition sequence of integrin αvβ6 ligands such as fibronectin. Almost all mAbs selectively reacted with integrin αvβ6 in the presence of divalent cations (Ca²⁺ and Mg²⁺) and blocked fibronectin–integrin αvβ6 binding. MAbs that shared the same heavy chain CDR3 amino acid sequence showed differences in reactivity to integrin αvβ6, indicating that the reactivity of these mAbs is also affected by the light chain. Some of the mAbs showed varying degrees of cross-reactivity with integrin αvβ3. The identification of shared CDR3 amino acid sequences in anti-integrin αvβ6 antibodies from several patients with UC suggests a common mechanism underlying their production, which may help elucidate the pathogenesis of UC.

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