Division of Neuro-Oncology, Department of Neurology, Hospital of the University of Pennsylvania, University of Pennsylvania, 3 W. Gates, 3400 Spruce Street, Philadelphia, PA 19104, USA.
Acta Neuropathol. 2009 Dec;118(6):737-43. doi: 10.1007/s00401-009-0582-4.
We report the immunopathological analysis of the brain and tumor of two patients who died of anti-NMDAR-associated encephalitis, and of the tumor of nine patients who recovered. Findings included prominent microgliosis and deposits of IgG with rare inflammatory infiltrates in the hippocampus, forebrain, basal ganglia, and spinal cord. Detection of cells expressing markers of cytotoxicity (TIA, granzyme B, perforin and Fas/Fas ligand) was extremely uncommon. All tumors showed NMDAR-expressing neurons and inflammatory infiltrates. All patients’ NMDAR antibodies were IgG1, IgG2, or IgG3. No complement deposits were observed in any of the central nervous system regions examined. Overall, these findings coupled with recently reported in vitro data showing that antibodies downregulate the levels of NMDA receptors suggest that the antibody immune-response is more relevant than cytotoxic T-cell mechanisms in the pathogenesis of anti-NMDAR-associated encephalitis.
我们报告了两名死于抗 NMDAR 相关脑炎的患者的脑部和肿瘤的免疫病理学分析，以及九名康复患者的肿瘤分析。结果包括海马体、前脑、基底神经节和脊髓中明显的小胶质细胞增生和 IgG 沉积，罕见炎症浸润。表达细胞毒性标志物（TIA、颗粒酶 B、穿孔素和 Fas/Fas 配体）的细胞极为罕见。所有肿瘤均显示 NMDAR 表达神经元和炎症浸润。所有患者的 NMDAR 抗体均为 IgG1、IgG2 或 IgG3。在检查的中枢神经系统区域均未观察到补体沉积。总的来说，这些发现与最近报道的体外数据表明，抗体下调 NMDA 受体的水平表明，在抗 NMDAR 相关脑炎的发病机制中，抗体免疫反应比细胞毒性 T 细胞机制更为重要。
