Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan.
Br J Cancer. 2024 May;130(9):1552-1560. doi: 10.1038/s41416-024-02647-1. Epub 2024 Mar 9.
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.
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.
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.
Anti-integrin αvβ6 autoantibodies may serve as potential biomarkers for the diagnosis, classification, risk management, and monitoring the disease activity, of ICI-induced colitis.
目前尚未确定免疫检查点抑制剂(ICI)诱导结肠炎的特异性生物标志物。此前,我们在>90%的溃疡性结肠炎(UC)患者中发现了抗整合素αvβ6 自身抗体。鉴于一部分 ICI 诱导的结肠炎与 UC 相似,我们旨在阐明这些自身抗体与 ICI 诱导的结肠炎之间的关系。
比较了 26 例 ICI 诱导的结肠炎患者和 157 例对照者的血清抗整合素αvβ6 自身抗体水平。对 ICI 诱导的结肠炎的内镜图像进行了中心审查。比较了 ICI 诱导的结肠炎患者抗整合素αvβ6 自身抗体的特征与 UC 患者的特征。
在 26 例 ICI 诱导的结肠炎患者中发现了 8 例(30.8%)存在抗整合素αvβ6 自身抗体,而在 157 例对照者中发现了 3 例(1.9%)(P<0.001)。具有抗整合素αvβ6 自身抗体的患者的内镜表现更典型,与无自身抗体的患者相比差异有统计学意义(P<0.001)。ICI 诱导的结肠炎患者的抗整合素αvβ6 自身抗体与≥3 级结肠炎(P=0.001)和激素抵抗(P=0.005)相关。抗整合素αvβ6 自身抗体滴度与 ICI 诱导的结肠炎疾病活动度相关。ICI 诱导的结肠炎的抗整合素αvβ6 自身抗体表现出与 UC 相似的特征。
抗整合素αvβ6 自身抗体可能作为 ICI 诱导结肠炎的诊断、分类、风险管理和监测疾病活动的潜在生物标志物。