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抗整合素 αvβ6 自身抗体是溃疡性结肠炎样免疫检查点抑制剂诱导结肠炎的潜在生物标志物。

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

机构信息

Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan.

出版信息

Br J Cancer. 2024 May;130(9):1552-1560. doi: 10.1038/s41416-024-02647-1. Epub 2024 Mar 9.

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.

摘要

背景

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。

方法

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。

结果

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。

结论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bcd/11058246/7927b7597643/41416_2024_2647_Fig1_HTML.jpg

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