Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Department of Immunology, UT Southwestern Medical Center, Dallas, TX, United States.
Front Immunol. 2023 Dec 12;14:1322818. doi: 10.3389/fimmu.2023.1322818. eCollection 2023.
The roles of preexisting auto-reactive antibodies in immune-related adverse events (irAEs) associated with immune checkpoint inhibitor therapy are not well defined. Here, we analyzed plasma samples longitudinally collected at predefined time points and at the time of irAEs from 58 patients with immunotherapy naïve metastatic non-small cell lung cancer treated on clinical protocol with ipilimumab and nivolumab. We used a proteomic microarray system capable of assaying antibody reactivity for IgG and IgM fractions against 120 antigens for systemically evaluating the correlations between auto-reactive antibodies and certain organ-specific irAEs. We found that distinct patterns of auto-reactive antibodies at baseline were associated with the subsequent development of organ-specific irAEs. Notably, ACHRG IgM was associated with pneumonitis, anti-cytokeratin 19 IgM with dermatitis, and anti-thyroglobulin IgG with hepatitis. These antibodies merit further investigation as potential biomarkers for identifying high-risk populations for irAEs and/or monitoring irAEs during immunotherapy treatment.
ClinicalTrials.gov identifier: NCT03391869.
预先存在的自身反应性抗体在免疫检查点抑制剂治疗相关的免疫相关不良事件（irAEs）中的作用尚未明确。在这里，我们分析了 58 名免疫治疗初治转移性非小细胞肺癌患者的血浆样本，这些患者按照临床方案接受伊匹单抗和纳武单抗治疗，并在预先设定的时间点和 irAE 时进行了纵向采集。我们使用了一种能够检测 IgG 和 IgM 分数对 120 种抗原反应性的蛋白质组微阵列系统，对自身反应性抗体与特定器官特异性 irAE 之间的相关性进行系统评估。我们发现基线时不同的自身反应性抗体模式与随后发生的器官特异性 irAE 有关。值得注意的是，ACHRG IgM 与肺炎有关，抗细胞角蛋白 19 IgM 与皮炎有关，抗甲状腺球蛋白 IgG 与肝炎有关。这些抗体值得进一步研究，作为识别 irAE 高危人群的潜在生物标志物，或在免疫治疗期间监测 irAE。
ClinicalTrials.gov 标识符：NCT03391869。
