Anti-integrin αvβ6 autoantibodies are a potential biomarker for ulcerative colitis-like immune checkpoint inhibitor-induced colitis

Author:

Yokode MasatakaORCID,Shiokawa MasahiroORCID,Kawakami HisatoORCID,Kuwada Takeshi,Nishikawa Yoshihiro,Muramoto Yuya,Kitamoto Hiroki,Okabe Makoto,Yamazaki Hajime,Okamoto Norihiro,Morita Toshihiro,Ohno Kazuya,Nakanishi Risa,Takimoto Ikuhisa,Yasuda Muneji,Chikugo Koki,Matsumoto Shimpei,Yoshida Hiroyuki,Ota Sakiko,Nakamura Takeharu,Okada Hirokazu,Hirano Tomonori,Kakiuchi NobuyukiORCID,Matsumori Tomoaki,Yamamoto Shuji,Uza Norimitsu,Ooi Makoto,Kodama Yuzo,Chiba Tsutomu,Hayashi HidetoshiORCID,Seno Hiroshi

Abstract

Abstract Background No specific biomarker for immune checkpoint inhibitor (ICI)-induced colitis has been established. Previously, we identified anti-integrin αvβ6 autoantibodies in >90% of patients with ulcerative colitis (UC). Given that a subset of ICI-induced colitis is similar to UC, we aimed to clarify the relationship between such autoantibodies and ICI-induced colitis. Methods Serum anti-integrin αvβ6 autoantibody levels were compared between 26 patients with ICI-induced colitis and 157 controls. Endoscopic images of ICI-induced colitis were centrally reviewed. Characteristics of anti-integrin αvβ6 autoantibodies in the ICI-induced colitis patients were compared with those of UC patients. Results Anti-integrin αvβ6 autoantibodies were found in 8/26 (30.8%) patients with ICI-induced colitis and 3/157 (1.9%) controls (P < 0.001). Patients with anti-integrin αvβ6 autoantibodies had significantly more typical UC endoscopic features than those without the autoantibodies (P < 0.001). Anti-integrin αvβ6 autoantibodies in ICI-induced colitis patients were associated with grade ≥3 colitis (P = 0.001) and steroid resistance (P = 0.005). Anti-integrin αvβ6 autoantibody titers correlated with ICI-induced colitis disease activity. Anti-integrin αvβ6 autoantibodies of ICI-induced colitis exhibited similar characteristics to those of UC. Conclusions Anti-integrin αvβ6 autoantibodies may serve as potential biomarkers for the diagnosis, classification, risk management, and monitoring the disease activity, of ICI-induced colitis.

Funder

the Japanese Society of Gastroenterology

MEXT | Japan Society for the Promotion of Science

Publisher

Springer Science and Business Media LLC

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