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
{"title":"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","authors":"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","doi":"10.1111/cns.70042","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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).</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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, <i>p</i> < 0.001; NFL: 549.11 [162.08–2462.61] vs 214.18 [81.60–349.60] pg/mL, <i>p</i> = 0.002). GFAP levels decreased in DNAP (<i>n</i> = 5) after immunotherapy (2446.75 [1583.45–6277.33] vs 1380.46 [272.16–2005.80] pg/mL, <i>p</i> = 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, <i>p</i> = 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.</p>\n </section>\n \n <section>\n \n <h3> Discussion</h3>\n \n <p>There are unidentified astrocyte antibodies. The manifestations of double-negativity are heterogeneous; nevertheless, the pathology and biomarkers remain consistent with astrocytopathy. Immunotherapy is effective.</p>\n </section>\n </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70042","citationCount":"0","resultStr":"{\"title\":\"Autoimmune astrocytopathy double negative for AQP4-IgG and GFAP-IgG: Retrospective research of clinical practice, biomarkers, and pathology\",\"authors\":\"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\",\"doi\":\"10.1111/cns.70042\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>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).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>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, <i>p</i> < 0.001; NFL: 549.11 [162.08–2462.61] vs 214.18 [81.60–349.60] pg/mL, <i>p</i> = 0.002). GFAP levels decreased in DNAP (<i>n</i> = 5) after immunotherapy (2446.75 [1583.45–6277.33] vs 1380.46 [272.16–2005.80] pg/mL, <i>p</i> = 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, <i>p</i> = 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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Discussion</h3>\\n \\n <p>There are unidentified astrocyte antibodies. The manifestations of double-negativity are heterogeneous; nevertheless, the pathology and biomarkers remain consistent with astrocytopathy. Immunotherapy is effective.</p>\\n </section>\\n </div>\",\"PeriodicalId\":154,\"journal\":{\"name\":\"CNS Neuroscience & Therapeutics\",\"volume\":\"30 9\",\"pages\":\"\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-09-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70042\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CNS Neuroscience & Therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/cns.70042\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS Neuroscience & Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cns.70042","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Autoimmune astrocytopathy double negative for AQP4-IgG and GFAP-IgG: Retrospective research of clinical practice, biomarkers, and pathology
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.
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.
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