脑脊液中14-3-3蛋白水平作为水通道蛋白4抗体阳性视神经脊髓炎谱系障碍的神经轴突生物标志物
Cerebrospinal 14-3-3 Protein Levels as a Neuroaxonal Biomarker in Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder.
作者信息
Villacieros-Álvarez Javier, Sepulveda Maria, Valls-Carbó Adrián, Fissolo Nicolas, Dinoto Alessandro, Fernández Victoria, Vilaseca Andreu, Arrambide Georgina, Gutierrez Lucia, Castillo Mireia, Bollo Luca, Espejo Carmen, Llufriu Sara, Blanco Yolanda, Armangue Thais, Álvarez Bravo Gary, Quiroga-Varela Ana, Ramió Torrentà Lluís, Cobo-Calvo Alvaro, Tintore Mar, Lünemann Jan D, Saiz Albert, Mariotto Sara, Montalban Xavier, Comabella Manuel
机构信息
Neurology-Neuroimmunology Department, Multiple Sclerosis Center of Catalonia, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Research Institute, Barcelona, Spain.
Universitat Autònoma de Barcelona (UAB), Spain.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2025 Sep;12(5):e200432. doi: 10.1212/NXI.0000000000200432. Epub 2025 Jun 30.
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], = 0.001) and MOGAD (3,112.95 [2,367.37-3,889.43], = 0.004). Patients with AQP4-NMOSD presenting with optic neuritis had lower 14-3-3 levels compared with those with other phenotypes ( < 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], = 0.003) and predicted final EDSS ≥ 6.0 (odds ratio 9.48 [1.69; 194.34]; = 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).
背景与目的
研究脑脊液14-3-3蛋白水平能否区分水通道蛋白4抗体阳性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）及多发性硬化（MS），以及AQP4-NMOSD患者脑脊液14-3-3蛋白水平与临床特征的相关性。
方法
这是一项对AQP4-NMOSD、MOGAD和MS患者进行的多中心回顾性队列研究，这些患者均有可用的脑脊液样本。采用酶联免疫吸附测定法（ELISA）对14-3-3蛋白水平进行定量，并在这三种疾病状态之间进行比较。在AQP4-NMOSD患者中，探讨脑脊液14-3-3蛋白水平与残疾结局之间的相关性。
结果
共纳入134例患者（AQP4-NMOSD，29例；MOGAD，43例；MS，62例）。与MS患者（3169.86[2522.65-3748.57]，P = 0.001）和MOGAD患者（3112.95[2367.37-3889.43]，P = 0.004）相比，AQP4-NMOSD患者的14-3-3蛋白水平更高（中位数[四分位间距]为4441.37[3240.05-11526.41]任意单位（AU）/mL）。与其他表型的AQP4-NMOSD患者相比，表现为视神经炎的患者14-3-3水平较低（P<0.001）。在AQP4-NMOSD中，14-3-3水平与发作时的扩展残疾状态量表（EDSS）相关（β[95%置信区间]为0.33[0.15-0.52]，P = 0.003），并可预测脊髓炎患者最终EDSS≥6.0（比值比为9.48[1.69；194.34]；P = 0.041）。
讨论
该研究表明，脑脊液14-3-3蛋白水平可能作为AQP4-NMOSD神经轴突损伤的生物标志物，因为它能够与疾病严重程度相关，并预测临床恢复不佳。
证据分类
本研究提供IV级证据，表明在表现为急性脊髓炎的个体中，脑脊液14-3-3可将AQP4-NMOSD与MS或MOGAD区分开来，敏感性为0.60（0.30-0.80），特异性为0.95（0.84-1.00）。
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