HLA class II allele DRB1*16:02 is associated with anti-NMDAR encephalitis
HLA class II allele DRB1*16:02 is associated with anti-NMDAR encephalitis
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HLA II 类等位基因 DRB116:02 与抗 NMDAR 脑炎相关
DOI：
10.1136/jnnp-2018-319714
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发表时间：
2019-06-01
影响因子：
11
通讯作者：
Yu, Xinhua
中科院分区：
文献类型：
--
作者：
Shu, Yaqing;Qiu, Wei;Yu, Xinhua
背景与目的抗N-甲基-D-天冬氨酸受体（anti-NMDAR）脑炎是最常见的自身免疫性脑炎，其病因和发病机制尚不清楚。方法对61例抗NMDAR脑炎患者和571例健康对照者的HLA基因型进行分析。结果抗NMDAR脑炎患者的DRB 1 *16：02等位基因与抗NMDAR脑炎相关（OR 3.416，95% CI 1.817 ~ 6.174，p=8.9x10（-5），p（adj）=0.021），患者组等位基因频率（14.75%）高于对照组（4.82%）。这种关联被认为是独立的肿瘤形成。除了疾病易感性，DRB 1 *16：02还与治疗期间患者的临床结果相关，其中具有DRB 1 *16：02的患者对治疗的治疗反应低于具有其他HLA等位基因的患者（p=0.033）。应用HLA肽结合预测算法和计算对接技术进行生物信息学分析，结果表明NMDAR的NR 1亚基与DRB 1 *16：02之间存在密切关系。结论本研究首次证实了特异性HLA-II类等位基因与抗NMDAR脑炎的相关性，为揭示该病的发病机制提供了新的思路。
Background and objective Aetiology and pathogenesis of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, the most common autoimmune encephalitis, is largely unknown. Since an association of the disease with the human leucocyte antigen (HLA) has not been shown so far, we here investigated whether anti-NMDAR encephalitis is associated with the HLA locus.Methods HLA loci of 61 patients with anti-NMDAR encephalitis and 571 healthy controls from the Chinese Han population were genotyped and analysed for this study.Results Our results show that the DRB1*16:02 allele is associated with anti-NMDAR encephalitis (OR 3.416, 95% CI 1.817 to 6.174, p=8.9x10(-5), p(adj)=0.021), with a higher allele frequency in patients (14.75%) than in controls (4.82%). This association was found to be independent of tumour formation. Besides disease susceptibility, DRB1*16:02 is also related to the clinical outcome of patients during treatment, where patients with DRB1*16:02 showed a lower therapeutic response to the treatment than patients with other HLA alleles (p=0.033). Bioinformatic analysis using HLA peptide-binding prediction algorithms and computational docking suggested a close relationship between the NR1 subunit of NMDAR and the DRB1*16:02.Conclusions This study for the first time demonstrates an association between specific HLA class II alleles and anti-NMDAR encephalitis, providing novel insights into the pathomechanism of the disease.