Autoimmune astrocytopathy double negative for AQP4-IgG and GFAP-IgG: Retrospective research of clinical practice, biomarkers, and pathology

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2024-09-15 DOI:10.1111/cns.70042

Pei-Hao Lin, Hai-Yan Yao, Li Huang, Cong-Cong Fu, Xiao-Li Yao, Chun Lian, Shi-Feng Zhang, Wen-Dong Lai, Guan-Yan Lin, Sha Liao, Jie Yang, Zhi-Feng Mao, Ding Liu, Bao-Yi Long, Jia-Jia Yue, Cong Gao, You-Ming Long

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引用次数: 0

Abstract

Objective

The objective of this study is to investigate the presence of astrocyte antibodies in patients, excluding aquaporin-4 or glial fibrillary acidic protein (GFAP) antibodies, while evaluating associated biomarkers and pathologies.

Methods

Patient serum and cerebrospinal fluid (CSF) were tested for antibodies using tissue- and cell-based assays. Neurofilament light chain (NFL) and GFAP in the CSF were detected using single-molecule array (SIMOA).

Results

116 patients accepted SIMOA. Fifteen functional neurological disorders patients without antibodies were designated as controls. Thirty-five patients were positive for astrocyte antibodies (Anti-GFAP: 7; Anti-AQP4: 7; unknown antibodies: 21, designed as the double-negative group, DNAP). The most frequent phenotype of DNAP was encephalitis (42.9%), followed by myelitis (23.8%), movement disorders (19.0%), and amyotrophic lateral sclerosis-like (ALS-like) disease (14.2%). The levels of CSF GFAP and NFL in DNAP were higher than in the control (GFAP: 1967.29 [776.60–13214.47] vs 475.38 [16.80–943.60] pg/mL, p < 0.001; NFL: 549.11 [162.08–2462.61] vs 214.18 [81.60–349.60] pg/mL, p = 0.002). GFAP levels decreased in DNAP (n = 5) after immunotherapy (2446.75 [1583.45–6277.33] vs 1380.46 [272.16–2005.80] pg/mL, p = 0.043), while there was no difference in NFL levels (2273.78 [162.08–2462.61] vs 890.42 [645.06–3168.06] pg/mL, p = 0.893). Two brain biopsy patterns were observed: one exhibited prominent tissue proliferation and hypertrophic astrocytes, with local loss of astrocytes, while the other showed severe astrocyte depletion with loss of neurofilaments around the vessels. Eighteen patients received immunotherapy, and improved except one with ALS-like symptoms. We identified anti-vimentin in this patient.

Discussion

There are unidentified astrocyte antibodies. The manifestations of double-negativity are heterogeneous; nevertheless, the pathology and biomarkers remain consistent with astrocytopathy. Immunotherapy is effective.

Abstract Image

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AQP4-IgG和GFAP-IgG双阴性的自身免疫性星形细胞病：临床实践、生物标志物和病理学回顾性研究

目的本研究旨在调查患者体内是否存在星形胶质细胞抗体，但不包括水蒸蛋白-4 或胶质纤维酸性蛋白（GFAP）抗体，同时评估相关的生物标记物和病理变化。方法使用基于组织和细胞的检测方法检测患者血清和脑脊液（CSF）中的抗体。使用单分子阵列（SIMOA）检测 CSF 中的神经丝蛋白轻链（NFL）和 GFAP。结果 116 名患者接受了 SIMOA。15 名无抗体的功能性神经紊乱患者被指定为对照组。35 名患者的星形胶质细胞抗体呈阳性（抗 GFAP：7 人；抗 AQP4：7 人；未知抗体：21 人，被设计为双阴性组，即 DNAP）。DNAP 最常见的表型是脑炎（42.9%），其次是脊髓炎（23.8%）、运动障碍（19.0%）和肌萎缩性脊髓侧索硬化症样（ALS）疾病（14.2%）。DNAP 的 CSF GFAP 和 NFL 水平高于对照组（GFAP：1967.29 [776.60-13214.47] vs 475.38 [16.80-943.60] pg/mL，p < 0.001；NFL：549.11 [162.08-2462.61] vs 214.18 [81.60-349.60] pg/mL，p = 0.002）。免疫治疗后，DNAP（n = 5）的 GFAP 水平下降（2446.75 [1583.45-6277.33] vs 1380.46 [272.16-2005.80] pg/mL，p = 0.043），而 NFL 水平没有差异（2273.78 [162.08-2462.61] vs 890.42 [645.06-3168.06] pg/mL，p = 0.893）。观察到两种脑活检模式：一种表现为突出的组织增生和肥大星形胶质细胞，局部星形胶质细胞缺失；另一种表现为严重的星形胶质细胞耗竭，血管周围的神经丝缺失。18 名患者接受了免疫治疗，除一名患者出现类似 ALS 的症状外，其他患者的病情均有所好转。我们在这名患者体内发现了抗波形蛋白。讨论存在不明的星形胶质细胞抗体。双阴性的表现不尽相同，但病理和生物标志物与星形胶质细胞病一致。免疫疗法是有效的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.