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髓鞘少突胶质细胞糖蛋白抗体相关疾病中神经元和胶质血清生物标志物的评估:MULTIMOGAD研究

Assessment of neuronal and glial serum biomarkers in myelin oligodendrocyte glycoprotein antibody-associated disease: the MULTIMOGAD study.

作者信息

Marignier Romain, Villacieros-Álvarez Javier, Espejo Carmen, Arrambide Georgin, Fissolo Nicolás, Gutiérrez Lucía, Dinoto Alessandro, Mulero Patricia, Rubio-Flores Laura, Nieto Pablo, Alcalá Carmen, Meca-Lallana Jose E, Martínez-Garcia Pedro, Millán Jorge, Bernard-Valnet Raphaël, González Inés, Orvíz García Aida, Tellez Raquel, Navarro Laura, Presas-Rodríguez Silvia, Romero-Pinel Lucía, Martínez-Yélamos Sergio, Cuello Juan Pablo, Alonso Torres Ana Maria, Piñar Raquel, Álvarez Bravo Gary, Benyahya Lakhdar, Trouillet-Assant Sophie, Dyon-Tafani Virginie, Froment Tilikete Caroline, Ruet Aurelie, Bourre Bertrand, Deschamps Romain, Papeix Caroline, Maillart Elisabeth, Kerschen Philippe, Ayrignac Xavier, Rovira Alex, Auger Cristina, Audoin Bertrand, Montalban Xavier, Tintore Mar, Mariotto Sara, Cobo-Calvo Alvaro

机构信息

Hospices Civils de Lyon, Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation-Hôpital Neurologique Pierre Wertheimer, Bron Cedex, France.

Neurology Department, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain.

出版信息

J Neurol Neurosurg Psychiatry. 2025 Aug 14;96(9):884-892. doi: 10.1136/jnnp-2024-335137.

DOI:10.1136/jnnp-2024-335137
PMID:39939136
Abstract

BACKGROUND

Serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) have emerged as important biomarkers in multiple sclerosis (MS) and aquaporin-4 seropositive neuromyelitis optica spectrum disorder (AQP4-NMOSD). However, their interest in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) remains unclear. Our aim was to characterise sNfL and sGFAP profile and analyse their usefulness in predicting relapses and disability in MOGAD.

METHODS

Retrospective study of adult MOGAD patients with serum samples collected at baseline (≤3 months from disease onset) and follow-up (>6 months from baseline sample). sNfL and sGFAP were analysed using Simoa HD-1, and values were compared across time-points. The association between biomarkers and clinical variables and their predictive value for disability and relapses were analysed.

RESULTS

Eighty-nine MOGAD patients were included. Baseline sNfL and sGFAP values were high at baseline and decreased over time (p<0.001, p=0.027, respectively). sNfL and sGFAP values were associated with Expanded Disability Status Scale (EDSS) at attacks (β 0.15 (0.06; 0.25), p=0.002; β 0.14 (0.07; 0.21), p<0.001, respectively) and were lower in optic neuritis presentations (β -0.69 (-1.18; -0.19), p=0.007; β -0.42 (-0.76; -0.08), p=0.016). Biomarker deltas[Δ] (baseline values - second samples values) were associated with ΔEDSS (initial EDSS - final EDSS) (ΔsNfL β 0.52 (0.01; 1.04), p=0.046; ΔsGFAP β 1.07 (0.38; 1.75), p=0.003). Finally, sNfL values independently predicted the risk of relapses (HR 2.06 (1.41; 3.01), p<0.001).

CONCLUSIONS

Our results on sNfL and sGFAP suggest initial neuro-axonal and astrocytic damage in MOGAD and the utility of these biomarkers at onset and follow-up in predicting clinical recovery and relapses.

摘要

背景

血清神经丝轻链(sNfL)和血清胶质纤维酸性蛋白(sGFAP)已成为多发性硬化症(MS)和水通道蛋白4血清阳性视神经脊髓炎谱系障碍(AQP4-NMOSD)的重要生物标志物。然而,它们在髓鞘少突胶质细胞糖蛋白抗体相关疾病(MOGAD)中的意义仍不明确。我们的目的是描述sNfL和sGFAP的特征,并分析它们在预测MOGAD复发和残疾方面的作用。

方法

对成年MOGAD患者进行回顾性研究,收集基线(疾病发作后≤3个月)和随访(距基线样本>6个月)时的血清样本。使用Simoa HD-1分析sNfL和sGFAP,并比较不同时间点的值。分析生物标志物与临床变量之间的关联及其对残疾和复发的预测价值。

结果

纳入89例MOGAD患者。基线时sNfL和sGFAP值较高,且随时间下降(分别为p<0.001,p=0.027)。发作时sNfL和sGFAP值与扩展残疾状态量表(EDSS)相关(β 0.15(0.06;0.25),p=0.002;β 0.14(0.07;0.21),p<0.001),在视神经炎表现中较低(β -0.69(-1.18;-0.19),p=0.007;β -0.42(-0.76;-0.08),p=0.016)。生物标志物变化量[Δ](基线值 - 第二次样本值)与ΔEDSS(初始EDSS - 最终EDSS)相关(ΔsNfL β 0.52(0.01;1.04),p=0.046;ΔsGFAP β 1.07(0.38;1.75),p=0.003)。最后,sNfL值独立预测复发风险(HR 2.06(1.41;3.01),p<0.001)。

结论

我们关于sNfL和sGFAP的研究结果表明MOGAD最初存在神经轴突和星形细胞损伤,以及这些生物标志物在发病时和随访中对预测临床恢复和复发的作用。

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