Cytomegalovirus immune responses are associated with lower serum NfL and disability accumulation risk at multiple sclerosis onset.

IF 4.8 2区医学 Q1 CLINICAL NEUROLOGY Multiple Sclerosis Journal Pub Date : 2024-09-09 DOI:10.1177/13524585241274571

Jan D Lünemann, Augusto Sao Avilés, Mar Tintoré, Luciana Midaglia, Nicolás Fissolo, Lucía Gutiérrez, Heinz Wiendl, Xavier Montalban, Manuel Comabella

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Abstract

Background: Infection by cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) play a prognostic role in multiple sclerosis (MS).

Objectives: To explore whether humoral immune responses to HCMV and EBV at disease onset were associated with changes in serum and cerebrospinal fluid (CSF) levels of inflammatory and neurodegeneration biomarkers.

Methods: Ninety-eight MS patients with a median follow-up of 20 years were included in the study. The levels of a panel of nine biomarkers were measured in serum (N = 60) and CSF (N = 61) samples of patients at the time of the first demyelinating event.

Results: Immune responses to HCMV inversely correlated with serum neurofilament light chain (sNfL) levels (rho = -0.367; p = 0.039). sNfL levels were reduced in patients with high immune responses to HCMV (p = 0.006). Elevated sNfL levels were associated with higher risk of Expanded Disability Status Scale (EDSS) 3.0 (p = 0.016), 4.0 (p = 0.009) and 6.0 (p = 0.003), and with higher risk of developing secondary progressive MS (p = 0.003) and to receive treatment (p = 0.032). Serum soluble CD21 levels were increased in patients with high immune responses to EBV nuclear antigen 1 (p = 0.020).

Conclusions: High immune responses to HCMV are associated with limited disease progression and central nervous system (CNS) injury in MS patients. These findings reinforce the protective role of HCMV infection in MS.

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巨细胞病毒免疫反应与多发性硬化症发病时较低的血清 NfL 和残疾累积风险有关。

背景：巨细胞病毒（HCMV）和爱泼斯坦-巴尔病毒（EBV）感染在多发性硬化症（MS）的预后中起着重要作用：目的：探讨发病时对 HCMV 和 EBV 的体液免疫反应是否与血清和脑脊液（CSF）中炎症和神经变性生物标志物水平的变化有关：研究共纳入了 98 名多发性硬化症患者，中位随访时间为 20 年。在首次发生脱髓鞘事件时，对患者的血清（60 例）和脑脊液（61 例）样本中的九种生物标记物水平进行了测定：对HCMV的免疫反应与血清神经丝蛋白轻链（sNfL）水平成反比（rho = -0.367；p = 0.039）。sNfL水平升高与残疾状况扩展量表（EDSS）3.0（p = 0.016）、4.0（p = 0.009）和6.0（p = 0.003）的风险较高、患继发性进展型多发性硬化症（p = 0.003）和接受治疗（p = 0.032）的风险较高有关。EBV核抗原1免疫反应高的患者血清可溶性CD21水平升高（p = 0.020）：结论：对 HCMV 的高免疫反应与多发性硬化症患者有限的疾病进展和中枢神经系统（CNS）损伤有关。这些发现加强了 HCMV 感染在多发性硬化症中的保护作用。

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

Multiple Sclerosis Journal 医学-临床神经学

CiteScore

10.90

自引率

6.90%

发文量

186

审稿时长

3-8 weeks

期刊介绍： Multiple Sclerosis Journal is a peer-reviewed international journal that focuses on all aspects of multiple sclerosis, neuromyelitis optica and other related autoimmune diseases of the central nervous system. The journal for your research in the following areas: * __Biologic basis:__ pathology, myelin biology, pathophysiology of the blood/brain barrier, axo-glial pathobiology, remyelination, virology and microbiome, immunology, proteomics * __Epidemology and genetics:__ genetics epigenetics, epidemiology * __Clinical and Neuroimaging:__ clinical neurology, biomarkers, neuroimaging and clinical outcome measures * __Therapeutics and rehabilitation:__ therapeutics, rehabilitation, psychology, neuroplasticity, neuroprotection, and systematic management Print ISSN: 1352-4585