1. Academic Validation
  2. Anti-integrin αvβ6 autoantibodies are a potential biomarker for ulcerative colitis-like immune checkpoint inhibitor-induced colitis

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

  • Br J Cancer. 2024 May;130(9):1552-1560. doi: 10.1038/s41416-024-02647-1.
Masataka Yokode 1 Masahiro Shiokawa # 2 Hisato Kawakami # 3 Takeshi Kuwada 1 Yoshihiro Nishikawa 1 Yuya Muramoto 1 Hiroki Kitamoto 1 Makoto Okabe 1 Hajime Yamazaki 4 Norihiro Okamoto 5 Toshihiro Morita 6 Kazuya Ohno 7 Risa Nakanishi 1 Ikuhisa Takimoto 1 Muneji Yasuda 1 Koki Chikugo 1 Shimpei Matsumoto 1 Hiroyuki Yoshida 1 Sakiko Ota 1 Takeharu Nakamura 1 Hirokazu Okada 1 Tomonori Hirano 1 Nobuyuki Kakiuchi 1 Tomoaki Matsumori 1 Shuji Yamamoto 1 Norimitsu Uza 1 Makoto Ooi 5 Yuzo Kodama 5 Tsutomu Chiba 8 Hidetoshi Hayashi 9 Hiroshi Seno 1
Affiliations

Affiliations

  • 1 Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • 2 Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan. [email protected].
  • 3 Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan. [email protected].
  • 4 Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • 5 Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan.
  • 6 Department of Gastroenterology and Hepatology, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan.
  • 7 Department of Gastroenterology, Shizuoka General Hospital, Shizuoka, Japan.
  • 8 Department of Gastroenterology and Hepatology, Kansai Electric Power Hospital, Osaka, Japan.
  • 9 Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan.
  • # Contributed equally.
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.

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