Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand.
Department of Pediatrics, Buriram Hospital, Buriram, Thailand.
Pediatr Neurol. 2022 Sep;134:93-99. doi: 10.1016/j.pediatrneurol.2022.06.014. Epub 2022 Jun 26.
Anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDARE) is one of the most common types of autoimmune encephalitis. Most patients have no apparent immunologic triggers, which suggests a genetic predisposition. This study was conducted to identify human leukocyte antigen (HLA) class II alleles associated with anti-NMDARE in Thai children.
This case-control study enrolled patients younger than 18 years who were diagnosed with anti-NMDARE between January 2010 and December 2020. A "good outcome" was determined as a patient with a modified Rankin scale score of less than 2 at any follow-up visit. HLA genotypes were determined at four-digit alleles using reverse sequence-specific oligonucleotide probe hybridization. The HLA class II allele frequency in patients was compared with that in a database of 101 healthy control Thai children.
Thirty-four patients were enrolled with a mean age of 12.8 ± 5.6 years (females 85.3%). The HLA-DRB1∗1502 allele frequency was significantly higher in patients than in controls (odds ratio, 2.32; 95% confidence interval, 1.11-4.8, P = 0.023). A good outcome was noted in 14 of 14 (100%) HLA-DRB1∗1502-positive patients (median time to a good outcome, 6 months) and 14 of 17 (82.3%) HLA-DRB1∗1502-negative patients (median time to a good outcome, 3 months). Two (11.8%) HLA-DRB1∗1502-positive patients had one relapse each, and six (35.3%) HLA-DRB1∗1502-negative patients had one to three relapses.
HLA-DRB1∗1502 was significantly associated with anti-NMDARE in our patients. Most patients had good outcomes. HLA-DRB1∗1502-positive patients tended to require a longer time to achieve a good outcome but had less frequent relapses than HLA-DRB1∗1502-negative patients.
抗 N-甲基-D-天冬氨酸受体脑炎（抗 NMDARE）是最常见的自身免疫性脑炎类型之一。大多数患者没有明显的免疫触发因素，这表明存在遗传易感性。本研究旨在鉴定与泰国儿童抗 NMDARE 相关的人类白细胞抗原（HLA）Ⅱ类等位基因。
本病例对照研究纳入了 2010 年 1 月至 2020 年 12 月期间诊断为抗 NMDARE 的年龄小于 18 岁的患者。改良 Rankin 量表评分在任何随访时均<2 分被确定为“良好结局”。采用反向序列特异性寡核苷酸探针杂交技术，在四位数等位基因水平上确定 HLA 基因型。将患者的 HLA Ⅱ类等位基因频率与 101 名健康泰国对照儿童的数据库进行比较。
共纳入 34 例患者，平均年龄为 12.8±5.6 岁（女性占 85.3%）。与对照组相比，患者 HLA-DRB1∗1502 等位基因频率明显更高（比值比，2.32；95%置信区间，1.11-4.8，P=0.023）。14 例 HLA-DRB1∗1502 阳性患者（中位良好结局时间为 6 个月）和 17 例 HLA-DRB1∗1502 阴性患者（中位良好结局时间为 3 个月）中各有 14 例（100%）结局良好。2 例（11.8%）HLA-DRB1∗1502 阳性患者各有 1 次复发，6 例（35.3%）HLA-DRB1∗1502 阴性患者有 1 至 3 次复发。
在本研究患者中，HLA-DRB1∗1502 与抗 NMDARE 显著相关。大多数患者结局良好。与 HLA-DRB1∗1502 阴性患者相比，HLA-DRB1∗1502 阳性患者达到良好结局的时间较长，但复发频率较低。
