Association of Levels of CSF Osteopontin With Cortical Atrophy and Disability in Early Multiple Sclerosis.

IF 7.8 1区医学 Q1 CLINICAL NEUROLOGY

Neurology® Neuroimmunology & Neuroinflammation Pub Date : 2024-09-01 Epub Date: 2024-06-25 DOI:10.1212/NXI.0000000000200265

Damiano Marastoni, Ermanna Turano, Agnese Tamanti, Elisa Colato, Anna Isabella Pisani, Arianna Scartezzini, Silvia Carotenuto, Valentina Mazziotti, Valentina Camera, Daniela Anni, Stefano Ziccardi, Maddalena Guandalini, Francesca B Pizzini, Federica Virla, Raffaella Mariotti, Roberta Magliozzi, Bruno Bonetti, Lawrence Steinman, Massimiliano Calabrese

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引用次数: 0

Abstract

Background and objectives: To evaluate CSF inflammatory markers with accumulation of cortical damage as well as disease activity in patients with early relapsing-remitting MS (RRMS).

Methods: CSF levels of osteopontin (OPN) and 66 inflammatory markers were assessed using an immune-assay multiplex technique in 107 patients with RRMS (82 F/25 M, mean age 35.7 ± 11.8 years). All patients underwent regular clinical assessment and yearly 3T MRI scans for 2 years while 39 patients had a 4-year follow-up. White matter lesion number and volume, cortical lesions (CLs) and volume, and global cortical thickness (CTh) were evaluated together with the 'no evidence of disease activity' (NEDA-3) status, defined by no relapses, no disability worsening, and no MRI activity, including CLs.

Results: The random forest algorithm selected OPN, CXCL13, TWEAK, TNF, IL19, sCD30, sTNFR1, IL35, IL16, and sCD163 as significantly associated with changes in global CTh. OPN and CXCL13 were most related to accumulation of atrophy after 2 and 4 years. In a multivariate linear regression model on CSF markers, OPN (p < 0.001), CXCL13 (p = 0.001), and sTNFR1 (p = 0.024) were increased in those patients with accumulating atrophy (adjusted R-squared 0.615). The 10 markers were added in a model that included all clinical, demographic, and MRI variables: OPN (p = 0.002) and IL19 (p = 0.022) levels were confirmed to be significantly increased in patients developing more CTh change over the follow-up (adjusted R-squared 0.619). CXCL13 and OPN also revealed the best association with NEDA-3 after 2 years, with OPN significantly linked to disability accumulation (OR 2.468 [1.46-5.034], p = 0.004) at the multivariate logistic regression model.

Discussion: These data confirm and expand our knowledge on the prognostic role of the CSF inflammatory profile in predicting changes in cortical pathology and disease activity in early MS. The data emphasize a crucial role of OPN.

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CSF 骨蛋白水平与早期多发性硬化症皮质萎缩和残疾的关系

背景和目的：评估早期复发缓解型多发性硬化症（RRMS）患者脑脊液炎症标志物与皮质损伤累积以及疾病活动的关系：评估早期复发缓解型多发性硬化症（RRMS）患者脑脊液炎症标志物与皮质损伤累积以及疾病活动的关系：方法：采用免疫测定多重技术评估107例RRMS患者（82例女性/25例男性，平均年龄（35.7 ± 11.8））的脑脊液骨生成素（OPN）和66种炎症标志物的水平。所有患者均接受了为期 2 年的定期临床评估和每年一次的 3T 磁共振成像扫描，其中 39 名患者接受了为期 4 年的随访。在评估白质病变数量和体积、皮质病变（CLs）和体积、整体皮质厚度（CTh）的同时，还评估了 "无疾病活动证据"（NEDA-3）状态，即无复发、无残疾恶化、无磁共振成像活动（包括CLs）：随机森林算法筛选出 OPN、CXCL13、TWEAK、TNF、IL19、sCD30、sTNFR1、IL35、IL16 和 sCD163 与总体 CTh 的变化显著相关。OPN 和 CXCL13 与 2 年和 4 年后的萎缩累积关系最大。在 CSF 标记物的多变量线性回归模型中，OPN（p < 0.001）、CXCL13（p = 0.001）和 sTNFR1（p = 0.024）在萎缩累积的患者中增加（调整后 R 平方为 0.615）。这 10 个标记物被添加到一个包含所有临床、人口统计学和 MRI 变量的模型中：OPN（p = 0.002）和IL19（p = 0.022）水平被证实在随访期间出现更多 CTh 变化的患者中显著增加（调整后 R 平方为 0.619）。在多变量逻辑回归模型中，CXCL13和OPN与2年后的NEDA-3的关系最为密切，其中OPN与残疾累积有明显联系（OR 2.468 [1.46-5.034]，p = 0.004）：这些数据证实并扩展了我们对 CSF 炎症特征在预测早期多发性硬化症皮质病理变化和疾病活动性方面的预后作用的认识。这些数据强调了OPN的关键作用。

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

Neurology® Neuroimmunology & Neuroinflammation Neuroscience-Neurology

CiteScore

15.60

自引率

2.30%

发文量

219

审稿时长

8 weeks

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.