Profiling peripheral blood oxidative stress in multiple sclerosis

IF 3 3区医学 Q2 CLINICAL NEUROLOGY

Multiple sclerosis and related disorders Pub Date : 2026-04-01 Epub Date: 2026-01-30 DOI:10.1016/j.msard.2026.107039

Thomas Minton , Kelly Hares , Kevin Kemp , Juliana Redondo , Neil J Scolding , Claire M Rice

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引用次数: 0

Abstract

Background

Oxidative stress is implicated in the pathophysiology of multiple sclerosis (MS), but the potential of oxidative stress responses as MS biomarkers has not been systematically explored.

Methods

Over 12 months, we measured serial plasma concentrations or activity, and peripheral blood mononuclear cell (PBMC) expression of master antioxidant regulators, downstream antioxidant enzymes, and plasma end products of oxidation in blood from people with MS (pwMS), including a cohort commencing disease modifying therapy (DMT). Multivariable regression models were employed adjusting for age, sex, disease duration, smoking, and repeated measures.

Results

40 control subjects and 78 pwMS participants (53 relapsing-remitting MS (RRMS), 11 primary progressive MS (PPMS) & 14 secondary progressive MS (SPMS)) were included; 12 commenced dimethyl fumarate (DMF), 12 ocrelizumab and 7 natalizumab. NFE2L2 (nuclear factor erythroid 2-related factor 2; Nrf2), CAT (catalase) and GPX1 (glutathione peroxidase 1) expression were downregulated in SPMS, with increased concentration of end products of oxidation. Plasma peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) concentration was higher in pwMS. Nrf2 concentration, catalase activity and PBMC SOD1 expression increased with DMF. PBMC NFE2L2, GPX1 and SOD1 expression increased with natalizumab. Effect sizes were relatively modest and inter-individual heterogeneity was high limiting potential clinical application. No significant associations with the Expanded Disability Status Scale were observed.

Conclusions

Our data support dysregulated oxidative stress responses in MS but individual oxidative stress components are unlikely to inform disease stratification and monitoring. However, a constellation of biomarkers, may have clinical utility and inform regarding MS pathophysiology and therapy.

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多发性硬化症外周血氧化应激分析。

背景：氧化应激与多发性硬化症（MS）的病理生理有关，但氧化应激反应作为MS生物标志物的潜力尚未得到系统的探索。方法：在12个月的时间里，我们测量了MS患者（pwMS）血液中主要抗氧化调节因子、下游抗氧化酶和血浆氧化终产物的一系列血浆浓度或活性、外周血单个核细胞（PBMC）表达，包括开始疾病修饰治疗（DMT）的队列。采用多变量回归模型调整年龄、性别、疾病持续时间、吸烟和重复测量。结果：纳入40名对照受试者和78名pwMS受试者(53名复发缓解型MS (RRMS)， 11名原发性进行性MS （PPMS）和14名继发性进行性MS (SPMS))；12人开始使用富马酸二甲酯（DMF）， 12人开始使用ocrelizumab， 7人开始使用natalizumab。NFE2L2（核因子-红细胞2相关因子2；Nrf2）、CAT（过氧化氢酶）和GPX1（谷胱甘肽过氧化物酶1）在SPMS中的表达下调，氧化终产物浓度升高。血浆过氧化物酶体增殖物激活受体γ辅助激活因子1- α (PGC-1α)浓度在pwMS中升高。Nrf2浓度、过氧化氢酶活性和PBMC SOD1表达随DMF升高而升高。PBMC NFE2L2、GPX1和SOD1表达随纳他珠单抗升高。效应量相对适中，个体间异质性很大，限制了潜在的临床应用。未观察到与扩展残疾状态量表有显著关联。结论：我们的数据支持MS中氧化应激反应失调，但个体氧化应激成分不太可能为疾病分层和监测提供信息。然而，一系列的生物标记物可能具有临床应用价值，并为多发性硬化症的病理生理和治疗提供信息。

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来源期刊

Multiple sclerosis and related disorders CLINICAL NEUROLOGY-

CiteScore

5.80

自引率

20.00%

发文量

814

审稿时长

66 days

期刊介绍： Multiple Sclerosis is an area of ever expanding research and escalating publications. Multiple Sclerosis and Related Disorders is a wide ranging international journal supported by key researchers from all neuroscience domains that focus on MS and associated disease of the central nervous system. The primary aim of this new journal is the rapid publication of high quality original research in the field. Important secondary aims will be timely updates and editorials on important scientific and clinical care advances, controversies in the field, and invited opinion articles from current thought leaders on topical issues. One section of the journal will focus on teaching, written to enhance the practice of community and academic neurologists involved in the care of MS patients. Summaries of key articles written for a lay audience will be provided as an on-line resource. A team of four chief editors is supported by leading section editors who will commission and appraise original and review articles concerning: clinical neurology, neuroimaging, neuropathology, neuroepidemiology, therapeutics, genetics / transcriptomics, experimental models, neuroimmunology, biomarkers, neuropsychology, neurorehabilitation, measurement scales, teaching, neuroethics and lay communication.