Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Priority Area Asthma and Allergy, Research Center Borstel, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Borstel, Germany.
J Neurol Neurosurg Psychiatry. 2019 Jun;90(6):652-658. doi: 10.1136/jnnp-2018-319714. Epub 2019 Jan 13.
Aetiology and pathogenesis of anti--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.
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.
Our results show that the allele is associated with anti-NMDAR encephalitis (OR 3.416, 95% CI 1.817 to 6.174, p=8.9×10, p=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, is also related to the clinical outcome of patients during treatment, where patients with 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 .
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.
抗 N-甲基-D-天冬氨酸受体（抗 NMDAR）脑炎是最常见的自身免疫性脑炎，其病因和发病机制在很大程度上尚不清楚。由于目前尚未显示该疾病与人类白细胞抗原（HLA）之间存在关联，因此我们在此研究中调查了抗 NMDAR 脑炎是否与 HLA 基因座相关。
本研究对 61 例抗 NMDAR 脑炎患者和 571 名来自中国汉族人群的健康对照者的 HLA 基因座进行了基因分型和分析。
我们的结果表明，等位基因与抗 NMDAR 脑炎相关（OR 3.416，95%CI 1.817 至 6.174，p=8.9×10，p=0.021），患者的等位基因频率（14.75%）高于对照组（4.82%）。这种关联独立于肿瘤形成。除了疾病易感性之外，还与患者治疗期间的临床结局有关，携带等位基因的患者对治疗的反应低于携带其他 HLA 等位基因的患者（p=0.033）。使用 HLA 肽结合预测算法和计算对接的生物信息学分析表明，NMDAR 的 NR1 亚基与之间存在密切关系。
本研究首次证明了特定 HLA Ⅱ类等位基因与抗 NMDAR 脑炎之间存在关联，为该疾病的发病机制提供了新的见解。
