《生命科学》 2026, 38(8): 1500-1516
自身抗体介导的神经免疫性脑疾病及精准诊疗
摘 要：
抗N-甲基-D-天冬氨酸（简称NMDA）受体脑炎是一种由自身抗体穿透血脑屏障，靶向神经细胞膜蛋白导致其功能障碍的神经自身免疫性疾病，常表现出认知障碍、癫痫、精神行为异常等症状。该病以患者的脑脊液及血清中检出抗NMDA受体自身抗体为关键生物标志物。本文系统回顾了抗NMDA受体脑炎的临床发现历程，重点阐述自身抗体介导疾病发生发展的致病机制，概述靶向性治疗研究的新进展，展望神经与免疫的交互研究将成为连接临床神经病学及基础神经科学的前沿交叉领域。
通讯作者：竺淑佳 , Email:zhusj@sustech.edu.cn
Abstract:
Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune neurological disorder characterized by pathogenic autoantibodies that cross the blood-brain barrier and target NMDA receptors on the neuronal cell surface. Clinically, patients present with a range of neuropsychiatric symptoms, including cognitive dysfunction, seizures, and prominent psychiatric and behavioral abnormalities. The detection of anti-NMDA receptor autoantibodies in cerebrospinal fluid and serum serves as the primary diagnostic biomarker. This review summarizes the clinical identification and discovery of anti-NMDA receptor encephalitis. Although anti-NMDA receptor encephalitis was initially recognized as an atypical neuropsychiatric disorder, its autoimmune etiology was subsequently established through multiple complementary approaches, including brain tissue immunostaining, neuronal labeling, and cell-based assays, ultimately effectively identifying NMDA receptors as the specific target antigen. Regarding clinical management, early first-line immunotherapy combined with tumor resection improves prognosis, while the initiation of second-line immunotherapy in patients with an inadequate response to first-line treatment can further reduce the recurrence. Furthermore, we highlight the pathological and neuronal mechanisms underlying the initiation and progression of anti-NMDA receptor encephalitis. Various triggering factors have been implicated in disrupting immune tolerance and promoting the production of pathogenic autoantibodies,
including tumor-associated immune responses and infection-induced immune dysregulation. Both in vitro and in vivo evidence supports the central pathogenic role of anti-NMDA receptor autoantibodies. These antibodies induce NMDA receptor cross-linking and internalization, disrupt excitatory synaptic transmission, and impair neural network function, thereby contributing to the diverse clinical manifestations observed in patients. Finally, we discuss recent advances in precision therapies, including neutralizing antibodies that competitively inhibit autoantibody function, as well as innovative cellular therapies utilizing chimeric autoantibody
receptor (CAAR) T cells to selectively eliminate the B cells expressing pathological antibodies. We anticipate that the interdisciplinary research on the nervous and immune systems will bridge the gap between clinical neurology and fundamental neuroscience, ultimately reshaping clinical treatment strategies for antibody-mediated neurological diseases.
Communication Author：ZHU Shu-Jia , Email:zhusj@sustech.edu.cn
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