From the Neuroimmunology Program (E.M.-H., M.G., A.G.-S., E.M., H.A., T.A., A.S., F.G., J.D.), Institut d'Investigacions Biomediques August Pi i Sunyer; Neurology Department (E.M.-H., M.G., H.A., M.S., T.A., A.S., J.D.), Hospital Clinic, and Pediatric Neuroimmunology Unit (T.A.), Sant Joan de Deu Children's Hospital, University of Barcelona; Centro de Investigaciones Biomedicas en Red de Enfermedades Raras (E.M.-H., M.G., T.A., J.D.), Madrid, Spain; Hospital Cayetano Heredia (A.P.R.), San Martin de Porres, Perú; Hadassah-Hebrew University Medical Center (T.B.-H.), Jerusalem, Israel; Department of Neurology (T.I.), Kitasato University School of Medicine, Sagamihara, Japan; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (J.D.), Barcelona, Spain.
Neurology. 2020 Jun 2;94(22):e2302-e2310. doi: 10.1212/WNL.0000000000009239. Epub 2020 Mar 11.
To determine the frequency and significance of concurrent glial (glial-Ab) or neuronal-surface (NS-Ab) antibodies in patients with anti-NMDA receptor (NMDAR) encephalitis.
Patients were identified during initial routine screening of a cohort (C1) of 646 patients consecutively diagnosed with anti-NMDAR encephalitis and another cohort (C2) of 200 patients systematically rescreened. Antibodies were determined with rat brain immunostaining and cell-based assays.
Concurrent antibodies were identified in 42 patients (4% from C1 and 7.5% from C2): 30 (71%) with glial-Ab and 12 (29%) with NS-Ab. Glial-Ab included myelin oligodendrocyte glycoprotein (MOG) (57%), glial fibrillary acidic protein (GFAP) (33%), and aquaporin 4 (AQP4) (10%). NS-Ab included AMPA receptor (AMPAR) (50%), GABAa receptor (GABAaR) (42%), and GABAb receptor (8%). In 39 (95%) of 41 patients, concurrent antibodies were detected in CSF, and in 17 (41%), concurrent antibodies were undetectable in serum. On routine clinical-immunologic studies, the presence of MOG-Ab and AQP4-Ab was suggested by previous episodes of encephalitis or demyelinating disorders (8, 27%), current clinical-radiologic features (e.g., optic neuritis, white matter changes), or standard rat brain immunohistochemistry (e.g., AQP4 reactivity). GFAP-Ab did not associate with distinct clinical-radiologic features. NS-Ab were suggested by MRI findings (e.g., medial temporal lobe changes [AMPAR-Ab], or multifocal cortico-subcortical abnormalities [GABAaR-Ab]), uncommon comorbid conditions (e.g., recent herpesvirus encephalitis), atypical tumors (e.g., breast cancer, neuroblastoma), or rat brain immunostaining. Patients with NS-Ab were less likely to have substantial recovery than those with glial-Ab (5 of 10 [50%] vs 17 of 19 [89%], = 0.03).
Between 4% and 7.5% of patients with anti-NMDAR encephalitis have concurrent glial-Ab or NS-Ab. Some of these antibodies (MOG-Ab, AQP4-Ab, NS-Ab) confer additional clinical-radiologic features and may influence prognosis.
确定抗 N-甲基-D-天冬氨酸受体（NMDAR）脑炎患者中同时存在神经胶质（胶质-Ab）或神经元表面（NS-Ab）抗体的频率和意义。
在连续诊断为抗 NMDAR 脑炎的 646 例患者队列（C1）和系统重新筛查的 200 例患者队列（C2）的初步常规筛查期间确定患者。使用大鼠脑组织免疫染色和基于细胞的测定法测定抗体。
在 42 例患者中发现了同时存在的抗体（C1 中为 4%，C2 中为 7.5%）：30 例（71%）为胶质-Ab，12 例（29%）为 NS-Ab。胶质-Ab 包括髓鞘少突胶质细胞糖蛋白（MOG）（57%）、神经胶质纤维酸性蛋白（GFAP）（33%）和水通道蛋白 4（AQP4）（10%）。NS-Ab 包括 AMPA 受体（AMPAR）（50%）、GABAa 受体（GABAaR）（42%）和 GABAb 受体（8%）。在 41 例患者中的 39 例（95%）中，CSF 中检测到同时存在的抗体，在 17 例患者（41%）中，血清中未检测到同时存在的抗体。在常规临床免疫研究中，先前的脑炎或脱髓鞘疾病（8 例，27%）、当前的临床-放射学特征（例如视神经炎、白质改变）或标准大鼠脑组织免疫组化（例如 AQP4 反应性）提示存在 MOG-Ab 和 AQP4-Ab。GFAP-Ab 与独特的临床-放射学特征无关。MRI 发现（例如，内侧颞叶改变[AMPAR-Ab]或多灶性皮质下异常[GABAaR-Ab]）、罕见的合并症（例如，近期单纯疱疹病毒性脑炎）、非典型肿瘤（例如，乳腺癌、神经母细胞瘤）或大鼠脑组织免疫染色提示存在 NS-Ab。与存在胶质-Ab 的患者相比，存在 NS-Ab 的患者不太可能有实质性恢复（10 例中有 5 例[50%]与 19 例中有 17 例[89%]，=0.03）。
在抗 NMDAR 脑炎患者中，有 4%至 7.5%同时存在神经胶质-Ab 或 NS-Ab。这些抗体中的一些（MOG-Ab、AQP4-Ab、NS-Ab）具有额外的临床-放射学特征，可能影响预后。
