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
  • 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.
PMID: 38461170 DOI: 10.1038/s41416-024-02647-1
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.