抗NMDA受体自身免疫性脑炎的易感性与免疫致病机制研究

神经系统副肿瘤综合征（PNS）是一类因肿瘤免疫介导的神经系统损害症群。抗NMDA受体脑炎是目前最常见的自身免疫性脑炎，病情危重，有潜在的致死风险。作为一种自身免疫性PNS， 抗NMDA受体的自身抗体的产生是关键致病因素，但抗体产生机制以及自身抗体导致的持续性炎症的免疫调控机制还不明确。本研究利用本课题组收集的病例资料和标本，研究抗NMDA受体脑炎病人中枢神经系统和全身的免疫细胞、炎性细胞因子和趋化因子的变化，以及人群中自身抗体产生的遗传易感性。并以临床数据为切入点，利用抗NMDA受体脑炎的小鼠动物模型，通过炎性细胞的转录组与炎症信号转导通路分析，在分子水平研究自身抗体及免疫细胞导致神经系统损伤的免疫致病机制。并进一步探索抗NMDA受体脑炎发展过程中，B细胞浸润及其相关趋化因子参与神经系统损伤的作用和分子调控机制，为今后寻找有效的免疫治疗方法和筛查诊断方案提供理论依据和潜在靶标。

Paraneoplastic neurologic syndromes (PNS) are a large group of neurological disorders mediated by immune response against tumor. However, the mechanisms of PNS remain unclear. As a kind of PNS, anti-NMDA receptor encephalitis is the most common autoimmune encephalitis so far, with critical conditions and potential lethal risks. As a kind of autoimmune disease, the production of autoantibodies against NMDA receptor is the key pathogenesis. However, the immunological mechanisms of autoantibody production and constant local inflammation in anti-NMDA receptor encephalitis are largely unknown. This study will utilize the clinical data and samples collected by our group, to investigate the variations of immune cells, inflammatory cytokines and chemokines in central nervous system and peripheral blood of the anti-NMDA receptor encephalitis patients, along with the genetic susceptibility to production of autoantibodies in the population. Moreover, through establishing mouse model of anti-NMDA receptor encephalitis and analyzing transcriptome and inflammatory signal transduction pathways of innate immune cells, we will explore the molecular mechanisms of nervous inflammation and damage induced by autoantibodies and their related immune cells. Furthermore, we will reveal the effect of B cells infiltration and the related chemokines on nervous system injury and the underlying molecular mechanisms. This study may provide new mechanisms and potential targets for the effective diagnosis and immunotherapy of anti-NMDA receptor encephalitis.