The Role of Antibodies in the Pathogenesis of Multiple Sclerosis
Abstract
The presence of persistent intrathecal oligoclonal immunoglobulin G (IgG) bands (OCBs) and lesional IgG deposition are seminal features of multiple sclerosis (MS) disease pathology. Despite extensive investigations, the role of antibodies, the products of mature CD19+ B cells, in disease development is still controversial and under significant debate. Recent success of B cell depletion therapies has revealed that CD20+ B cells contribute to MS pathogenesis via both antigen-presentation and T-cell-regulation. However, the limited efficacy of CD20+ B cell depletion therapies for the treatment of progressive MS indicates that additional mechanisms are involved. In this review, we present findings suggesting a potential pathological role for increased intrathecal IgGs, the relation of circulating antibodies to intrathecal IgGs, and the selective elevation of IgG1 and IgG3 subclasses in MS. We propose a working hypothesis that circulating B cells and antibodies contribute significantly to intrathecal IgGs, thereby exerting primary and pathogenic effects in MS development. Increased levels of IgG1 and IgG3 antibodies induce potent antibody-mediated cytotoxicity to central nervous system (CNS) cells and/or reduce the threshold require...Continue Reading
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