The immunological role of exosomes in autoimmune encephalitis (AE) remains uncharacterized and not examined. In this study we ought to determine whether exosomes are generated in AE and to define the presence of cell surface neuronal autoantigens (autoAgs) in the cargo. Exosomes were isolated from cerebrospinal fluid (CSF) from 12 patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis, 8 patients with anti-gamma-aminobutyric acid-B (GABA_B) receptor encephalitis, 8 patients with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis, 8 patients with anti-contactin-associated protein-like 2 (CASPR2) encephalitis, 10 patients with anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 1,2 (AMPA) receptor encephalitis and 30 control individuals negative of antibodies against neuronal autoAgs. Western blot demonstrated that CSF or sera derived exosomes from AE contained specific neuronal autoAgs in protein aggregates, however, control subjects had no detectable levels of these neuronal autoAgs. In addition, development of antibodies against NMDAR, GABA_BR, LGI1, CASPR2, and AMPAR were detected in the sera after 30 days immunization of C57BL/6 J mice with exosomes isolated from antibody positive AE patients; Enzyme-linked immunospot (ELISpot) assay demonstrated increased frequency of neuronal autoAgs-specific IL-17 and IFN-γ in splenocytes from AE derived exosomes immunized mice. We concluded that exosomes expressing neuronal autoAgs were present in CSF from antibody positive AE patients, and we propose these exosomes carrying neuronal autoAgs would play an important role in the immune pathogenesis of autoimmune encephalitis.

外泌体在自身免疫性脑炎（AE）中的免疫作用仍未鉴定，也未进行检查。在这项研究中，我们应该确定是否在AE中产生外来体，并确定货物中细胞表面神经元自身抗原（autoAgs）的存在。从12例抗-N-甲基d-天冬氨酸（NMDA）受体脑炎患者，8例抗γ-氨基丁酸B（GABA _B）患者的脑脊液（CSF）中分离出外来体）受体脑炎，抗亮氨酸高神经胶质瘤灭活1（LGI1）脑炎8例，抗接触素相关蛋白样2（CASPR2）脑炎8例，抗α-氨基-3-羟基的10例-5-甲基-4-异恶唑丙酸1,2（AMPA）受体脑炎和30例针对神经元自身Ags抗体阴性的对照个体。Western印迹证明，AE的CSF或血清衍生的外泌体在蛋白质聚集物中包含特定的神经元自身Ag，但是，对照受试者没有这些神经元自身Ag的可检测水平。此外，还开发了针对NMDAR，GABA _B的抗体用分离自抗体阳性AE患者的外泌体免疫C57BL / 6 J小鼠30天后，在血清中检测到R，LGI1，CASPR2和AMPAR。酶联免疫斑点法（ELISpot）测定表明，来自AE衍生的外来体免疫小鼠的脾细胞中神经元自身Ags特异性IL-17和IFN-γ的频率增加。我们得出的结论是，抗体阳性的AE患者的CSF中存在表达神经元自身Ags的外泌体，并且我们建议这些携带神经元自身Ags的外泌体在自身免疫性脑炎的免疫发病机制中起重要作用。