自身免疫panel 作为免疫检查点抑制剂治疗患者毒性的预测因子（ALERT）。
Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT).
机构信息
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, ON, Canada.
出版信息
J Exp Clin Cancer Res. 2023 Oct 21;42(1):276. doi: 10.1186/s13046-023-02851-6.
BACKGROUND
Immune-checkpoint inhibitors (ICI) can lead to immune-related adverse events (irAEs) in a significant proportion of patients. The mechanisms underlying irAEs development are mostly unknown and might involve multiple immune effectors, such as T cells, B cells and autoantibodies (AutoAb).
METHODS
We used custom autoantigen (AutoAg) microarrays to profile AutoAb related to irAEs in patients receiving ICI. Plasma was collected before and after ICI from cancer patients participating in two clinical trials (NCT03686202, NCT02644369). A one-time collection was obtained from healthy controls for comparison. Custom arrays with 162 autoAg were used to detect IgG and IgM reactivities. Differences of median fluorescent intensity (MFI) were analyzed with Wilcoxon sign rank test and Kruskal-Wallis test. MFI 500 was used as threshold to define autoAb reactivity.
RESULTS
A total of 114 patients and 14 healthy controls were included in this study. irAEs of grade (G) ≥ 2 occurred in 37/114 patients (32%). We observed a greater number of IgG and IgM reactivities in pre-ICI collections from patients versus healthy controls (62 vs 32 p < 0.001). Patients experiencing irAEs G ≥ 2 demonstrated pre-ICI IgG reactivity to a greater number of AutoAg than patients who did not develop irAEs (39 vs 33 p = 0.040). We observed post-treatment increase of IgM reactivities in subjects experiencing irAEs G ≥ 2 (29 vs 35, p = 0.021) and a decrease of IgG levels after steroids (38 vs 28, p = 0.009).
CONCLUSIONS
Overall, these results support the potential role of autoAb in irAEs etiology and evolution. A prospective study is ongoing to validate our findings (NCT04107311).
背景
免疫检查点抑制剂（ICI）可导致相当一部分患者出现免疫相关不良事件（irAEs）。irAEs 发展的机制大多尚不清楚，可能涉及多种免疫效应物，如 T 细胞、B 细胞和自身抗体（AutoAb）。
方法
我们使用定制的自身抗原（AutoAg）微阵列来分析接受 ICI 治疗的患者与 irAEs 相关的 AutoAb。从参加两项临床试验（NCT03686202，NCT02644369）的癌症患者在 ICI 前后采集血浆。为了进行比较，从健康对照者中获得一次性采集。使用带有 162 个 AutoAg 的定制阵列来检测 IgG 和 IgM 反应性。采用 Wilcoxon 符号秩检验和 Kruskal-Wallis 检验分析中位数荧光强度（MFI）的差异。使用 MFI 500 作为阈值来定义 AutoAb 反应性。
结果
本研究共纳入 114 例患者和 14 例健康对照者。37/114 例（32%）患者出现 G≥2 级 irAEs。与健康对照者相比，我们观察到患者在 ICI 前采集物中 IgG 和 IgM 反应性更多（62 比 32，p<0.001）。与未发生 irAEs 的患者相比，发生 G≥2 级 irAEs 的患者在 ICI 前 IgG 反应性检测到更多的 AutoAg（39 比 33，p=0.040）。我们观察到经历 G≥2 级 irAEs 的受试者在治疗后 IgM 反应性增加（29 比 35，p=0.021），并且在使用类固醇后 IgG 水平降低（38 比 28，p=0.009）。
结论
总的来说，这些结果支持自身抗体在 irAEs 发病机制和演变中的潜在作用。一项正在进行的前瞻性研究旨在验证我们的发现（NCT04107311）。
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