The Contribution of Complement System in Multiple Sclerosis: Mechanisms and Therapeutic Potentials.

Immunology

Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Zhejiang, Hangzhou, China.

Published: July 2025


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Article Abstract

The complement system has been described as playing key roles in both innate and adaptive immune responses. Multiple sclerosis (MS) is an autoimmune disease characterised by the destruction of myelinated axons in the central nervous system (CNS). In this review, we will discuss the possible role of the complement system in MS. Complement components have been found to be highly expressed in post-mortem brains and in blood and cerebrospinal fluid samples of MS patients. Though the use of knock-out mouse models, the specific roles of complement components have been further investigated. According to these studies, complement components have been found to play controversial roles in the pathogenesis of MS. We will discuss the roles of classical and alternative pathways, as well as the lectin pathway, of the complement system in MS. Anaphylatoxins including C3a and C5a were also found to contribute to the pathology of MS. In addition, studies regarding the complement components in blood and cerebrospinal fluid are presented, which may be useful for the prediction and assessment of MS as biomarkers. Overall, this review summarises the importance of the complement system's involvement in the pathology of MS, which may guide future therapeutic approaches to MS and provide potential biomarkers for MS diagnosis and prognosis.

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http://dx.doi.org/10.1111/imm.13929DOI Listing

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