Department of Neurology, Seoul National University Hospital, Seoul, Republic of Korea.
Department of Neurology, Konyang University Hospital, Deajeon, Republic of Korea.
Ann Clin Transl Neurol. 2020 Nov;7(11):2243-2250. doi: 10.1002/acn3.51213. Epub 2020 Oct 8.
While immune checkpoint inhibitors are increasingly used for various cancers, unpredictable immune-related adverse events (irAEs) such as autoimmune encephalitis is life-threatening. Here, we report an association between human leukocyte antigen (HLA) and atezolizumab-induced encephalitis.
From an institutional prospective cohort for encephalitis, we identified patients with autoimmune encephalitis after the use of atezolizumab, a PD-L1 (programmed death-ligand 1) inhibitor, from August 2016 to September 2019 and analyzed their HLA genotypes.
A total of 290 patients received atezolizumab, and seven patients developed autoimmune encephalitis, and five of whom were enrolled for the analysis. The patients presented altered mentality, seizures, or myelitis. Three patients had the HLA-B27:05 genotype in common (60%), which is significantly frequent given its low frequency in the general population (2.5%). After Bonferroni correction, HLA-B27:05 was significantly associated with autoimmune encephalitis by atezolizumab (corrected P < 0.001, odds ratio 59, 95% CI = 9.0 ~ 386.9).
Here we found that three in five patients with autoimmune encephalitis associated with atezolizumab had the rare HLA-B*27:05 genotype. Further systematic analyses in larger cohorts are necessary to investigate the value of HLA screening to prevent the life-threatening adverse events.
尽管免疫检查点抑制剂越来越多地用于各种癌症，但不可预测的免疫相关不良事件（irAEs），如自身免疫性脑炎，却具有致命风险。在这里，我们报告了人类白细胞抗原（HLA）与阿替利珠单抗引起的脑炎之间的关联。
我们从一个机构前瞻性脑炎队列中，确定了自 2016 年 8 月至 2019 年 9 月使用 PD-L1（程序性死亡配体 1）抑制剂阿替利珠单抗后发生自身免疫性脑炎的患者，并分析了他们的 HLA 基因型。
共有 290 例患者接受了阿替利珠单抗治疗，其中 7 例发生自身免疫性脑炎，其中 5 例纳入分析。患者表现为精神状态改变、癫痫发作或脊髓炎。有 3 例患者共同具有 HLA-B27:05 基因型（60%），这一频率显著高于其在普通人群中的低频（2.5%）。经过 Bonferroni 校正后，HLA-B27:05 与阿替利珠单抗引起的自身免疫性脑炎显著相关（校正 P<0.001，优势比 59，95%CI=9.0~386.9）。
在这里，我们发现与阿替利珠单抗相关的自身免疫性脑炎患者中有五分之三具有罕见的 HLA-B*27:05 基因型。在更大的队列中进行进一步的系统分析，以调查 HLA 筛查在预防危及生命的不良事件中的价值是必要的。
