Anti-NMDA receptor encephalitis was first described about thirteen years ago and has become one of the most important differential diagnoses for new-onset psychosis. The disease is mediated by autoantibodies against the subunit 1 of the N-methyl-D-aspartate receptor (NMDA-R1) in patients presenting with variable clinical symptoms. Patients often profit from immunmodulatory therapy, independent of their individual symptoms.

In this study CSF samples as well as monoclonal antibodies derived from patients diagnosed with NMDA-R1 encephalitis were applied to rat hippocampus and visualized by immunocytochemistry. This reveals at least two distinct patterns of immunoreactivity. Antibodies from “pattern group 1” display the familiar pattern of NMDA-R1 distribution in the hippocampus reported in experiments with rabbit anti-NMDA-R1 antibodies. Neurons and primary dendrites in the CA1 and CA3 region show strongly stained cell bodies, in line with the predominant postsynaptic localization of the NMDA receptor in the brain. However, autoantibodies from “pattern group 2” show an inverse pattern, with no staining of the cell bodies and primary dendrites in CA1 and CA3 regions. Electron microscopic experiments disclose that autoantibodies of “pattern group 1 patients” bind to postsynaptic NMDA receptors, while those of “pattern group 2 patients” target presynaptic NMDA receptors. We describe one NMDA-receptor antibody giving staining comparable to rabbit anti-NMDA-R1 antibodies, raised against the C-terminus. In the highly heterogenous disease anti-NMDA-receptor 1 encephalitis we found evidence for at least two different subtypes. It will be very interesting to determine whether there also are two distinct clinical phenotypes.

抗 NMDA 受体脑炎大约在 13 年前首次被描述，现已成为新发精神病最重要的鉴别诊断之一。该疾病是由针对 N-甲基-D-天冬氨酸受体 (NMDA-R1) 亚基 1 的自身抗体介导的，这些抗体存在于具有不同临床症状的患者中。患者通常受益于免疫调节治疗，而与他们的个体症状无关。

在这项研究中，将 CSF 样本以及来自诊断为 NMDA-R1 脑炎的患者的单克隆抗体应用于大鼠海马，并通过免疫细胞化学进行可视化。这揭示了至少两种不同的免疫反应模式。来自“模式组 1”的抗体显示了在兔抗 NMDA-R1 抗体实验中报告的海马中 NMDA-R1 分布的熟悉模式。CA1 和 CA3 区域的神经元和初级树突显示出强烈染色的细胞体，与大脑中 NMDA 受体的主要突触后定位一致。然而，来自“模式组 2”的自身抗体显示出相反的模式，CA1 和 CA3 区域的细胞体和初级树突没有染色。电子显微镜实验表明，“模式组 1 患者”的自身抗体与突触后 NMDA 受体结合，而“模式组 2 患者”的自身抗体则靶向突触前 NMDA 受体。我们描述了一种 NMDA 受体抗体，其染色效果与兔抗 NMDA-R1 抗体相当，针对 C 端产生。在高度异质性疾病抗 NMDA 受体 1 脑炎中，我们发现了至少两种不同亚型的证据。确定是否也存在两种不同的临床表型将是非常有趣的。在高度异质性疾病抗 NMDA 受体 1 脑炎中，我们发现了至少两种不同亚型的证据。确定是否也存在两种不同的临床表型将是非常有趣的。在高度异质性疾病抗 NMDA 受体 1 脑炎中，我们发现了至少两种不同亚型的证据。确定是否也存在两种不同的临床表型将是非常有趣的。