Clinical significance of anti-NMDAR concurrent with glial or neuronal surface antibodies
Clinical significance of anti-NMDAR concurrent with glial or neuronal surface antibodies
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DOI：
10.1212/wnl.0000000000009239
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发表时间：
2020-06-02
期刊：
影响因子：
9.9
通讯作者：
Dalmau, Josep
中科院分区：
文献类型：
--
作者：
Martinez-Hernandez, Eugenia;Guasp, Mar;Dalmau, Josep
目的 确定抗 NMDA 受体（NMDAR）脑炎患者中同时出现胶质细胞（胶质细胞抗体）或神经元表面（NS-Ab）抗体的频率和意义。方法 在对连续诊断为抗 NMDAR 脑炎的 646 名患者组成的队列 (C1) 和对 200 名经过系统重新筛查的患者组成的另一组 (C2) 进行初始常规筛查时确定患者。通过大鼠脑免疫染色和基于细胞的测定来测定抗体。结果 42 名患者（4% 来自 C1，7.5% 来自 C2）同时鉴定出抗体：30 名（71%）患有神经胶质抗体，12 名（29%）患有 NS-Ab。胶质细胞抗体包括髓鞘少突胶质细胞糖蛋白 (MOG) (57%)、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%)。 41 名患者中有 39 名（95%）在脑脊液中检测到了并发抗体，而在 17 名（41%）名患者中血清中未检测到并发抗体。在常规临床免疫学研究中，先前的脑炎或脱髓鞘疾病发作 (8, 27%)、当前的临床放射学特征（例如视神经炎、白质变化）或标准大鼠脑免疫组织化学（例如 AQP4 反应性）提示 MOG-Ab 和 AQP4-Ab 的存在。 GFAP-Ab 与独特的临床放射学特征无关。 NS-Ab 由 MRI 结果（例如，内侧颞叶变化 [AMPAR-Ab] 或多灶性皮质-皮质下异常 [GABAaR-Ab]）、不常见的合并症（例如，近期疱疹病毒脑炎）、非典型肿瘤（例如，乳腺癌、神经母细胞瘤）或大鼠脑免疫染色提示。与神经胶质抗体患者相比，患有 NS-Ab 的患者实质性康复的可能性较小（10 名患者中的 5 名 [50%] vs 19 名患者中的 17 名 [89%]，p= 0.03）。结论 4% 至 7.5% 的抗 NMDAR 脑炎患者同时存在神经胶质抗体或 NS-Ab。其中一些抗体（MOG-Ab、AQP4-Ab、NS-Ab）具有额外的临床放射学特征，并可能影响预后。
Objective 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. Methods 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. Results 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%],p= 0.03). Conclusions 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.