Javier Villacieros-Álvarez, Maria Sepulveda, Adrián Valls-Carbó, Nicolas Fissolo, Alessandro Dinoto, Victoria Fernández, Andreu Vilaseca, Georgina Arrambide, Lucia Gutierrez, Mireia Castillo, Luca Bollo, Carmen Espejo, Sara Llufriu, Yolanda Blanco, Thais Armangue, Gary Álvarez Bravo, Ana Quiroga-Varela, Lluís Ramió Torrentà, Alvaro Cobo-Calvo, Mar Tintore, Jan D Lünemann, Albert Saiz, Sara Mariotto, Xavier Montalban, Manuel Comabella
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In patients with AQP4-NMOSD, the association between CSF 14-3-3 protein levels and disability outcomes was explored.</p><p><strong>Results: </strong>A total of 134 patients were included (AQP4-NMOSD, n = 29; MOGAD, n = 43; MS, n = 62). Patients with AQP4-NMOSD had higher 14-3-3 protein levels (median [interquartile range] 4,441.37 [3,240.05-11526.41] arbitrary units (AU)/mL) compared with those with MS (3,169.86 [2,522.65-3,748.57], <i>p</i> = 0.001) and MOGAD (3,112.95 [2,367.37-3,889.43], <i>p</i> = 0.004). Patients with AQP4-NMOSD presenting with optic neuritis had lower 14-3-3 levels compared with those with other phenotypes (<i>p</i> < 0.001). In AQP4-NMOSD, 14-3-3 levels associated with Expanded Disability Status Scale (EDSS) at attack (β [95%CI] 0.33 [0.15-0.52], <i>p</i> = 0.003) and predicted final EDSS ≥ 6.0 (odds ratio 9.48 [1.69; 194.34]; <i>p</i> = 0.041) in patients with myelitis.</p><p><strong>Discussion: </strong>The study suggests a potential role of CSF 14-3-3 protein levels as a biomarker of neuroaxonal damage in AQP4-NMOSD, because of its ability to correlate with disease severity and predict poor clinical recovery.</p><p><strong>Classification of evidence: </strong>This study provides Class IV evidence that in individuals presenting with acute myelitis, CSF 14-3-3 differentiates AQP4-NMOSD from MS or MOGAD with a sensitivity of 0.60 (0.30-0.80) and specificity of 0.95 (0.84-1.00).</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 5","pages":"e200432"},"PeriodicalIF":7.8000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221159/pdf/","citationCount":"0","resultStr":"{\"title\":\"Cerebrospinal 14-3-3 Protein Levels as a Neuroaxonal Biomarker in Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder.\",\"authors\":\"Javier Villacieros-Álvarez, Maria Sepulveda, Adrián Valls-Carbó, Nicolas Fissolo, Alessandro Dinoto, Victoria Fernández, Andreu Vilaseca, Georgina Arrambide, Lucia Gutierrez, Mireia Castillo, Luca Bollo, Carmen Espejo, Sara Llufriu, Yolanda Blanco, Thais Armangue, Gary Álvarez Bravo, Ana Quiroga-Varela, Lluís Ramió Torrentà, Alvaro Cobo-Calvo, Mar Tintore, Jan D Lünemann, Albert Saiz, Sara Mariotto, Xavier Montalban, Manuel Comabella\",\"doi\":\"10.1212/NXI.0000000000200432\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objectives: </strong>To investigate whether CSF 14-3-3 protein levels discriminate aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) from myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and multiple sclerosis (MS) and the association of CSF 14-3-3 protein levels with clinical features in patients with AQP4-NMOSD.</p><p><strong>Methods: </strong>This was a multicentric retrospective cohort study of patients with AQP4-NMOSD, MOGAD, and MS, with available CSF samples. 14-3-3 protein levels were quantified using ELISA and compared between the 3 conditions. In patients with AQP4-NMOSD, the association between CSF 14-3-3 protein levels and disability outcomes was explored.</p><p><strong>Results: </strong>A total of 134 patients were included (AQP4-NMOSD, n = 29; MOGAD, n = 43; MS, n = 62). Patients with AQP4-NMOSD had higher 14-3-3 protein levels (median [interquartile range] 4,441.37 [3,240.05-11526.41] arbitrary units (AU)/mL) compared with those with MS (3,169.86 [2,522.65-3,748.57], <i>p</i> = 0.001) and MOGAD (3,112.95 [2,367.37-3,889.43], <i>p</i> = 0.004). Patients with AQP4-NMOSD presenting with optic neuritis had lower 14-3-3 levels compared with those with other phenotypes (<i>p</i> < 0.001). 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引用次数: 0
摘要
背景与目的：探讨脑脊液14-3-3蛋白水平是否能区分水通道蛋白-4抗体阳性的视神经脊髓炎谱系障碍（AQP4-NMOSD）与髓鞘少突胶质细胞糖蛋白抗体相关疾病（MOGAD）和多发性硬化症（MS），以及CSF 14-3-3蛋白水平与AQP4-NMOSD患者临床特征的关系。方法：这是一项多中心回顾性队列研究，纳入了AQP4-NMOSD、MOGAD和MS患者，并提供了可用的CSF样本。采用ELISA法定量测定14-3-3蛋白水平，并比较3种条件下的差异。在AQP4-NMOSD患者中，探讨CSF 14-3-3蛋白水平与残疾结局之间的关系。结果：共纳入134例患者(AQP4-NMOSD, n = 29；MOGAD, n = 43；MS, n = 62)。AQP4-NMOSD患者的14-3-3蛋白水平（中位数[四分位数间距]4,441.37[3,240.05-11526.41]任意单位(AU)/mL）高于MS （3,169.86 [2,522.65-3,748.57], p = 0.001）和MOGAD （3,112.95 [2,367.37-3,889.43], p = 0.004）。以视神经炎为表现的AQP4-NMOSD患者与其他表型患者相比，14-3-3水平较低（p < 0.001）。在AQP4-NMOSD中，14-3-3水平与发作时扩展残疾状态量表（EDSS）相关（β [95%CI] 0.33 [0.15-0.52], p = 0.003），预测最终EDSS≥6.0(优势比9.48 [1.69；194.34);P = 0.041)。讨论：该研究提示CSF 14-3-3蛋白水平作为AQP4-NMOSD神经轴突损伤的生物标志物的潜在作用，因为它能够与疾病严重程度相关，并预测临床恢复不良。证据分类：本研究提供IV类证据，在急性脊髓炎患者中，CSF 14-3-3区分AQP4-NMOSD与MS或MOGAD的敏感性为0.60(0.30-0.80)，特异性为0.95（0.84-1.00）。
Cerebrospinal 14-3-3 Protein Levels as a Neuroaxonal Biomarker in Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder.
Background and objectives: To investigate whether CSF 14-3-3 protein levels discriminate aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) from myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and multiple sclerosis (MS) and the association of CSF 14-3-3 protein levels with clinical features in patients with AQP4-NMOSD.
Methods: This was a multicentric retrospective cohort study of patients with AQP4-NMOSD, MOGAD, and MS, with available CSF samples. 14-3-3 protein levels were quantified using ELISA and compared between the 3 conditions. In patients with AQP4-NMOSD, the association between CSF 14-3-3 protein levels and disability outcomes was explored.
Results: A total of 134 patients were included (AQP4-NMOSD, n = 29; MOGAD, n = 43; MS, n = 62). Patients with AQP4-NMOSD had higher 14-3-3 protein levels (median [interquartile range] 4,441.37 [3,240.05-11526.41] arbitrary units (AU)/mL) compared with those with MS (3,169.86 [2,522.65-3,748.57], p = 0.001) and MOGAD (3,112.95 [2,367.37-3,889.43], p = 0.004). Patients with AQP4-NMOSD presenting with optic neuritis had lower 14-3-3 levels compared with those with other phenotypes (p < 0.001). In AQP4-NMOSD, 14-3-3 levels associated with Expanded Disability Status Scale (EDSS) at attack (β [95%CI] 0.33 [0.15-0.52], p = 0.003) and predicted final EDSS ≥ 6.0 (odds ratio 9.48 [1.69; 194.34]; p = 0.041) in patients with myelitis.
Discussion: The study suggests a potential role of CSF 14-3-3 protein levels as a biomarker of neuroaxonal damage in AQP4-NMOSD, because of its ability to correlate with disease severity and predict poor clinical recovery.
Classification of evidence: This study provides Class IV evidence that in individuals presenting with acute myelitis, CSF 14-3-3 differentiates AQP4-NMOSD from MS or MOGAD with a sensitivity of 0.60 (0.30-0.80) and specificity of 0.95 (0.84-1.00).
期刊介绍：
Neurology Neuroimmunology & Neuroinflammation is an official journal of the American Academy of Neurology. Neurology: Neuroimmunology & Neuroinflammation will be the premier peer-reviewed journal in neuroimmunology and neuroinflammation. This journal publishes rigorously peer-reviewed open-access reports of original research and in-depth reviews of topics in neuroimmunology & neuroinflammation, affecting the full range of neurologic diseases including (but not limited to) Alzheimer's disease, Parkinson's disease, ALS, tauopathy, and stroke; multiple sclerosis and NMO; inflammatory peripheral nerve and muscle disease, Guillain-Barré and myasthenia gravis; nervous system infection; paraneoplastic syndromes, noninfectious encephalitides and other antibody-mediated disorders; and psychiatric and neurodevelopmental disorders. Clinical trials, instructive case reports, and small case series will also be featured.
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