Anti-LGI1 encephalitis is associated with unique HLA subtypes
Anti-LGI1 encephalitis is associated with unique HLA subtypes
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DOI：
10.1002/ana.24860
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发表时间：
2017-02-01
影响因子：
11.2
通讯作者：
Chu, Kon
中科院分区：
文献类型：
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作者：
Kim, Tae-Joon;Lee, Soon-Tae;Chu, Kon
以抗-富含亮氨酸的胶质瘤灭活1（anti-leucine-rich glioma inactivated 1，anti-LGI 1）和抗-N-甲基-D-天冬氨酸受体（anti-NMDAR）脑炎为代表的自身免疫性脑炎（Autoimmune encephalitis，AE），近年来发现的神经元自身抗体，其临床意义日益增加。然而，其免疫发病机制尚未完全了解。在这里，我们调查AE是否与人类白细胞抗原（HLA）亚型有关。方法我们比较了11例抗LGI 1和17例抗NMDAR脑炎患者的HLA基因型与对照组，其中包括210例癫痫患者和485名健康韩国人。结果抗LGI 1脑炎与DRB 1 *07：01-DQB 1 *02：02单倍型有关（10例患者; 91%）在HLA II类基因中，以及在HLA I类区域中与B*44：03（8例患者; 73%）和C*07：06（7例患者; 64%）。抗LGI 1脑炎组中这些等位基因的检出率显著高于癫痫对照组和健康对照组。相反，抗NMDAR脑炎与HLA基因型无关。使用HLA-肽结合预测算法和计算对接的其他分析支持了密切的关系。InterpretationThis发现表明，大多数抗LGI 1脑炎的发展与特定的HLA亚型的人口，提供了一个新的疾病机制的见解。《神经病学年鉴》2017;81：183-192
ObjectiveAutoimmune encephalitis (AE), represented by anti-leucine-rich glioma-inactivated 1 (anti-LGI1) and anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, has increasing clinical significance based on recent discoveries of neuronal autoantibodies. However, its immunopathogenesis is not fully understood. Here, we investigated whether AE is associated with the human leukocyte antigen (HLA) subtypes.MethodsWe compared the HLA genotypes of 11 anti-LGI1 and 17 anti-NMDAR encephalitis patients to the control groups, which consisted of 210 epilepsy patients and 485 healthy Koreans.ResultsAnti-LGI1 encephalitis was associated with the DRB1*07:01-DQB1*02:02 haplotype (10 patients; 91%) in HLA class II genes, as well as with B*44:03 (8 patients; 73%) and C*07:06 (7 patients; 64%) in the HLA class I region. The prevalence of these alleles in anti-LGI1 encephalitis was significantly higher than that in the epilepsy controls or healthy controls. By contrast, anti-NMDAR encephalitis was not associated with HLA genotypes. Additional analysis using HLA-peptide binding prediction algorithms and computational docking underpinned the close relationship.InterpretationThis finding suggests that most anti-LGI1 encephalitis develops in a population with specific HLA subtypes, providing insight into a novel disease mechanism. Ann Neurol 2017;81:183-192