Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy A Novel Meningoencephalomyelitis
Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy A Novel Meningoencephalomyelitis
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DOI：
10.1001/jamaneurol.2016.2549
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发表时间：
2016-11-01
期刊：
影响因子：
29
通讯作者：
Lennon, Vanda A.
中科院分区：
文献类型：
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作者：
Fang, Boyan;McKeon, Andrew;Lennon, Vanda A.
一种新的星形细胞自身抗体已被确定为免疫治疗应答的复发性自身免疫性脑膜脑脊髓炎的生物标志物。血清阳性可将自身免疫胶质纤维酸性蛋白（GFAP）脑膜脑脊髓炎与通常用于鉴别诊断的疾病区分开来。目的描述一种在血清或脑脊液中发现的针对星形胶质细胞胞质中间丝蛋白的新型IgG自身抗体。设计、环境和参与者回顾性分析1998年10月15日至2016年4月1日在梅奥诊所神经免疫学实验室鉴定的血清阳性患者的医疗记录，对自身抗体谱进行盲法综合血清学评估，以帮助诊断神经系统自身免疫（并预测癌症可能性）。新的自身抗体的频率和定义、自身抗原的免疫化学鉴定、自身抗体的临床和磁共振成像相关性以及免疫治疗反应性。结果在103例可查阅病历的患者中，16例最初确定为血清阳性的患者是本研究的对象。出现神经症状的中位年龄为42岁（范围21-73岁）；没有性别优势。我们发现这种新的神经自身抗体是gmap特异性的，它是疾病谱限制的，但并不罕见（频率相当于浦肯野细胞抗体1型[抗- yo]）。其在小鼠组织上的丝状脑膜、脑室下和血管周围免疫染色模式类似于患者血管周围线性增强的特征性磁共振成像结果。主要临床表现为头痛、亚急性脑病、视神经乳头炎、炎症性脊髓炎、体位性震颤和小脑性共济失调。有资料显示，14例患者中有13例（93%）出现脑脊液炎症。16例患者中有6例（38%）在神经系统发病3年内被诊断为肿瘤：前列腺和胃食管腺癌、骨髓瘤、黑色素瘤、结肠类癌、腮腺多形性腺瘤和畸胎瘤。大剂量皮质类固醇治疗后神经系统改善，患者有复发倾向，但无长期免疫抑制。结论和相关性胶质原纤维酸性蛋白特异性IgG可识别一种独特的皮质类固醇反应性，有时是副肿瘤自身免疫性脑膜脑脊髓炎。它有一种致命的犬科疾病：坏死性脑膜脑炎。GFAP的表达已被报道在一些肿瘤类型中发现的副肿瘤病例。胶质纤维酸性蛋白肽特异性细胞毒性CD8(+) T细胞在自身免疫性GFAP脑膜脑炎转基因小鼠模型中作为效应物。
IMPORTANCE A novel astrocytic autoantibody has been identified as a biomarker of a relapsing autoimmune meningoencephalomyelitis that is immunotherapy responsive. Seropositivity distinguishes autoimmune glial fibrillary acidic protein (GFAP) meningoencephalomyelitis from disorders commonly considered in the differential diagnosis.OBJECTIVE To describe a novel IgG autoantibody found in serum or cerebrospinal fluid that is specific for a cytosolic intermediate filament protein of astrocytes.DESIGN, SETTING, AND PARTICIPANTS Retrospective review of the medical records of seropositive patients identified in the Mayo Clinic Neuroimmunology Laboratory from October 15, 1998, to April 1, 2016, in blinded comprehensive serologic evaluation for autoantibody profiles to aid the diagnosis of neurologic autoimmunity (and predict cancer likelihood).MAIN OUTCOMES AND MEASURES Frequency and definition of novel autoantibody, the autoantigen's immunochemical identification, clinical and magnetic resonance imaging correlations of the autoantibody, and immunotherapy responsiveness.RESULTS Of 103 patients whose medical records were available for review, the 16 initial patients identified as seropositive were the subject of this study. Median age at neurologic symptom onset was 42 years (range, 21-73 years); there was no sex predominance. The novel neural autoantibody, which we discovered to be GFAP-specific, is disease spectrum restricted but not rare (frequency equivalent to Purkinje cell antibody type 1 [anti-Yo]). Its filamentous pial, subventricular, and perivascular immunostaining pattern on mouse tissue resembles the characteristic magnetic resonance imaging findings of linear perivascular enhancement in patients. Prominent clinical manifestations are headache, subacute encephalopathy, optic papillitis, inflammatorymyelitis, postural tremor, and cerebellar ataxia. Cerebrospinal fluid was inflammatory in 13 of 14 patients (93%) with data available. Neoplasia was diagnosed within 3 years of neurologic onset in 6 of 16 patients (38%): prostate and gastroesophageal adenocarcinomas, myeloma, melanoma, colonic carcinoid, parotid pleomorphic adenoma, and teratoma. Neurologic improvement followed treatment with high-dose corticosteroids, with a tendency of patients to relapse without long-term immunosuppression.CONCLUSIONS AND RELEVANCE Glial fibrillary acidic protein-specific IgG identifies a distinctive, corticosteroid-responsive, sometimes paraneoplastic autoimmune meningoencephalomyelitis. It has a lethal canine equivalent: necrotizing meningoencephalitis. Expression of GFAP has been reported in some of the tumor types identified in paraneoplastic cases. Glial fibrillary acidic protein peptide-specific cytotoxic CD8(+) T cells are implicated as effectors in a transgenic mouse model of autoimmune GFAP meningoencephalitis.