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Title: Identification of an Anti–Integrin αvβ6 Autoantibody in Patients With Ulcerative Colitis
Authors: Kuwada, Takeshi
Shiokawa, Masahiro
Kodama, Yuzo
Ota, Sakiko
Kakiuchi, Nobuyuki
Nannya, Yasuhito
Yamazaki, Hajime  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-9034-4370 (unconfirmed)
Yoshida, Hiroyuki
Nakamura, Takeharu
Matsumoto, Shimpei
Muramoto, Yuya
Yamamoto, Shuji  kyouindb  KAKEN_id
Honzawa, Yusuke
Kuriyama, Katsutoshi
Okamoto, Kanako
Hirano, Tomonori
Okada, Hirokazu
Marui, Saiko
Sogabe, Yuko
Morita, Toshihiro
Matsumori, Tomoaki
Mima, Atsushi
Nishikawa, Yoshihiro
Ueda, Tatsuki
Matsumura, Kazuyoshi
Uza, Norimitsu  kyouindb  KAKEN_id
Chiba, Tsutomu
Seno, Hiroshi  kyouindb  KAKEN_id
Author's alias: 桒田, 威
塩川, 雅広
児玉, 裕三
太田, 彩貴子
垣内, 伸之
南谷, 泰仁
山崎, 大
中村, 武晴
村本, 雄哉
山本, 修司
本澤, 有介
栗山, 勝利
岡田, 浩和
丸井, 彩子
森田, 敏広
松森, 友昭
西川, 義浩
松村, 和宜
宇座, 徳光
千葉, 勉
妹尾, 浩
Keywords: Inflammatory Bowel Disease
Autoimmunity
Epithelial Adhesion Molecule
RGD Motif
Issue Date: Jul-2021
Publisher: Elsevier BV
Journal title: Gastroenterology
Volume: 160
Issue: 7
Start page: 2383
End page: 2394
Thesis number: e21
Abstract: Background and Aims: Ulcerative colitis is the most frequent type of inflammatory bowel disease and is characterized by colonic epithelial cell damage. Although involvement of autoimmunity has been suggested in ulcerative colitis, specific autoantigens/antibodies have yet to be elucidated. Methods: Using 23 recombinant integrin proteins, we performed enzyme-linked immunosorbent assays on sera from patients with ulcerative colitis and controls. Integrin expression and IgG binding in the colon tissues of patients with ulcerative colitis and controls were examined using immunofluorescence and coimmunoprecipitation, respectively. The blocking activity of autoantibodies was examined using solid-phase binding and cell adhesion assays. Results: Screening revealed that patients with ulcerative colitis had IgG antibodies against integrin αvβ6. In the training and validation groups, 103 of 112 (92.0%) patients with ulcerative colitis and only 8 of 155 (5.2%) controls had anti–integrin αvβ6 antibodies (P < .001), resulting in a sensitivity of 92.0% and a specificity of 94.8% for diagnosing ulcerative colitis. Anti–integrin αvβ6 antibody titers coincided with ulcerative colitis disease activity, and IgG1 was the major subclass. Patient IgG bound to the integrin αvβ6 expressed on colonic epithelial cells. Moreover, IgG of patients with ulcerative colitis blocked integrin αvβ6–fibronectin binding through an RGD (Arg-Gly-Asp) tripeptide motif and inhibited cell adhesion. Conclusions: A significant majority of patients with ulcerative colitis had autoantibodies against integrin αvβ6, which may serve as a potential diagnostic biomarker with high sensitivity and specificity.
Description: 指定難病「潰瘍性大腸炎」の自己抗体発見 --新たな診断や治療開発へ--. 京都大学プレスリリース. 2021-03-09.
Rights: © 2021 by the AGA Institute. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
URI: http://hdl.handle.net/2433/261943
DOI(Published Version): 10.1053/j.gastro.2021.02.019
PubMed ID: 33582126
Related Link: https://www.kyoto-u.ac.jp/ja/research-news/2021-03-09-1
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