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

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2024年3月9日

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

摘要

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.