Table_4_Single-cell transcriptomics reveals cell type–specific immune regulation associated with anti-NMDA receptor encephalitis in humans.xlsx

IntroductionAnti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is a rare autoimmune disease, and the peripheral immune characteristics associated with anti-NMDARE antibodies remain unclear.
MethodsHerein, we characterized peripheral blood mononuclear cells from patients with anti-NMDARE and healthy individuals by single-cell RNA sequencing (scRNA-seq).
ResultsThe transcriptional profiles of 129,217 cells were assessed, and 21 major cell clusters were identified. B-cell activation and differentiation, plasma cell expansion, and excessive inflammatory responses in innate immunity were all identified. Patients with anti-NMDARE showed higher expression levels of CXCL8, IL1B, IL6, TNF, TNFSF13, TNFSF13B, and NLRP3. We observed that anti-NMDARE patients in the acute phase expressed high levels of DC_CCR7 in human myeloid cells. Moreover, we observed that anti-NMDARE effects include oligoclonal expansions in response to immunizing agents. Strong humoral immunity and positive regulation of lymphocyte activation were observed in acute stage anti-NMDARE patients.
DiscussionThis high-dimensional single-cell profiling of the peripheral immune microenvironment suggests that potential mechanisms are involved in the pathogenesis and recovery of anti-NMDAREs.

引言
抗N-甲基-D-天冬氨酸受体脑炎（anti-N-methyl-D-aspartate receptor encephalitis, anti-NMDARE）是一种罕见的自身免疫性疾病，目前与抗NMDARE抗体相关的外周免疫特征仍不明确。
方法
本研究采用单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）技术，对抗NMDARE患者与健康对照个体的外周血单个核细胞进行了表征分析。
结果
本研究共分析了129,217个细胞的转录组表达谱，鉴定出21个主要细胞簇。研究发现，抗NMDARE患者体内存在B细胞活化与分化、浆细胞扩增以及先天免疫过度炎症反应等特征；患者外周血中CXCL8、IL1B、IL6、TNF、TNFSF13、TNFSF13B及NLRP3的表达水平显著升高。本研究观察到，急性期抗NMDARE患者的髓系细胞中DC_CCR7呈高表达状态；此外，抗NMDARE患者体内存在针对免疫原的寡克隆扩增现象；急性期抗NMDARE患者还表现出强烈的体液免疫应答以及淋巴细胞活化的正向调控特征。
讨论
本研究针对外周免疫微环境开展的高维单细胞测序分析，为阐明抗NMDARE的发病机制与疾病恢复过程提供了潜在的关键线索。