Immune Profiling of Encephalitis

项目总结 脑炎是一种由感染或自身免疫条件引起的脑部炎症性疾病。最多的 常见类型的自身免疫性脑炎(AE)与高滴度的N-甲基-D-脑炎抗体有关 天冬氨酸型谷氨酸受体(NMDAR)，称为αNMDAR-AE。抗NMDAR抗体结合，交联， 并内化NMDAR受体，导致神经元功能改变。清除抗NMDAR抗体有 因此是一线治疗的重点，但即使在接受治疗的患者中也会发生反复发作。 抗NMDAR抗体是由抗体分泌细胞(ASCs)产生的，ASCs来自记忆B细胞 游泳池。我们假设αNMDAR-AE患者的记忆B细胞和ASCs表达与 NMDAR。确定αNMDAR-AE患者的记忆B细胞池中存在高频率的 NMDAR反应性记忆B细胞将是理解NMDAR免疫发病机制的第一步。 αNMDAR-AE，并可能促使考虑有效消除NMDAR-AE的附加疗法。 反应性记忆B细胞在αNMDAR-AE患者治疗和管理中的早期应用

PROJECT SUMMARY Encephalitis is an inflammatory disease of the brain caused by infection or autoimmune conditions. The most common type of autoimmune encephalitis (AE) is associated with high titers of antibodies against N-methyl-D- aspartate type glutamate receptors (NMDARs), termed αNMDAR-AE. Anti-NMDAR antibodies bind, cross-link, and internalize NMDAR receptors leading to altered neuronal function. Removal of anti-NMDAR antibodies has thus been the focus of first-line therapy, but recurrent attacks occur even in treated patients. Anti-NMDAR antibodies are produced by antibody secreting cells (ASCs), which arise from the memory B cell pool. We hypothesize that memory B cells and ASCs of αNMDAR-AE patients express antibodies that bind to NMDARs. Establishing that the memory B cell pool of αNMDAR-AE patients harbors a high frequency of NMDAR-reactive memory B cells would be the first step towards understanding the immunopathogenesis of αNMDAR-AE, and may prompt consideration of additive therapies that would effectively remove NMDAR- reactive memory B cells early in the treatment and management of αNMDAR-AE patients.