Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is associated with IRF7, BANK1 and TBX21 polymorphisms in two populations
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is associated with IRF7, BANK1 and TBX21 polymorphisms in two populations
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两个人群中抗NMDAR脑炎与IRF7、BANK1和TBX21多态性相关
DOI：
10.1111/ene.14596
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发表时间：
2020-11-10
影响因子：
5.1
通讯作者：
Qiu, W.
中科院分区：
文献类型：
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作者：
Shu, Y.;Guo, J.;Qiu, W.
背景和目的针对抗N-甲基-D-天冬氨酸受体（NMDAR）GluN 1（NR 1）亚单位的自身抗体引起脑炎。尽管已经显示抗NMDAR脑炎与人类白细胞抗原（HLA）基因座相关，但HLA基因座之外的疾病易感基因仍然未被鉴定。在这项研究中，我们的目的是探讨抗NMDAR脑炎与非HLA基因的关联。方法从中国汉族人群中招募两个抗NMDAR脑炎队列。中国北方病例对照组包括98例患者和460例对照，而中国南方病例对照组包括78例患者和541例对照。所有参与者的基因分型为28个单核苷酸多态性，与自身免疫性疾病或传染病。结果在两个独立的病例对照组，我们确定了显着的关联，抗NMDAR脑炎与IRF 7 rs 1131665（比值比[OR] 3.34，95%置信区间[CI] 1.99-5.63; P < 0.000001，P调整= 0.00004），BANK 1 rs 4522865（OR 1.44，95% CI 1.15-1.82; P = 0.0017，P调整= 0.0149）和TBX 21 rs 17244587（OR 2.03，95% CI 1.35-3.05; P = 0.00051，P调整= 0.0066）。结论本研究首次发现了抗NMDAR脑炎的非HLA易感基因。IRF 7、BANK 1和TBX 21与抗NMDAR脑炎的相关性表明B细胞活化、Th 1应答、病毒感染和I型干扰素信号通路参与了疾病的发病机制。
Background and purpose Autoantibodies targeting the GluN1(NR1) subunit of the anti-N-methyl-D-aspartate receptor (NMDAR) cause encephalitis. Although it has been shown that anti-NMDAR encephalitis is associated with human leukocyte antigen (HLA) loci, susceptibility genes for the disease outside the HLA loci remain unidentified. In this study, we aimed to explore the association of anti-NMDAR encephalitis with non-HLA genes.Methods Two Chinese anti-NMDAR encephalitis cohorts from Han populations were recruited for this study. The North Chinese case-control set consisted of 98 patients and 460 controls, while the South Chinese case-control set included 78 patients and 541 controls. All participants were genotyped for 28 single nucleotide polymorphisms that are associated with autoimmune disorders or infectious diseases.Results In two independent case-control sets, we identified significant associations of anti-NMDAR encephalitis with IRF7 rs1131665 (odds ratio [OR] 3.34, 95% confidence interval [CI] 1.99-5.63; P < 0.000001, P-adjusted = 0.00004), BANK1 rs4522865 (OR 1.44, 95% CI 1.15-1.82; P = 0.0017, P-adjusted = 0.0149), and TBX21 rs17244587 (OR 2.03, 95% CI 1.35-3.05; P = 0.00051, P-adjusted = 0.0066). Furthermore, analysis of the three polymorphisms with clinical features of the disease revealed that the IRF7 rs1131665 was associated with tumor status.Conclusion The present study has for the first time identified non-HLA susceptibility genes for anti-NMDAR encephalitis. The association of IRF7, BANK1 and TBX21 with anti-NMDAR encephalitis suggests that B-cell activation, Th1 responses, virus infection and the type I interferon signaling pathway are involved in the pathogenesis of the disease.