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Effect of Multiple Sclerosis Disease-Modifying Therapies on B Cells and Humoral Immunity

Erin E. Longbrake, MD, PhD1; Anne H. Cross, MD1
[+] Author Affiliations
1Department of Neurology, Washington University, St Louis, Missouri
JAMA Neurol. 2016;73(2):219-225. doi:10.1001/jamaneurol.2015.3977.
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The unequivocal success of B-cell–depleting agents in reducing magnetic resonance imaging and clinical activity in therapeutic trials indicates that B cells play a vital role in mediating the clinical course of relapsing multiple sclerosis (MS). Although no agent that specifically targets B cells has yet been approved for clinical use, all existing disease-modifying therapies (DMTs) for MS modulate B-cell immunity to some degree. This review examines the effects of MS DMTs on B-cell immunity. Most MS DMTs induced a relative decrease in circulating memory B cells with concomitant expansion of circulating B-cell precursors and/or naive B cells. B-cell function was also altered; most DMTs induced B-cell production of the anti-inflammatory cytokine interleukin 10 while inhibiting B-cell expression of proinflammatory cytokines. The commonalities in the effects of approved DMTs on B-cell phenotype and function among treated patients with MS are striking and suggest that effects on B cells underlie part of their efficacy. More complete understanding of how the existing DMTs modulate B-cell immunity may identify future targets for therapeutic intervention.

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Figure.
Effect of Existing Multiple Sclerosis (MS) Disease-Modifying Therapies (DMTs) on B-Cell Immunity

Most MS DMTs slightly decrease the numbers of circulating B cells and shift the circulating B-cell population toward immature or naive cells. Most DMTs also lead to increased B-cell production of interleukin (IL) 10 with a concurrent decrease in proinflammatory cytokine production. Data on circulating B-cell immunophenotypes are not available for dimethyl fumarate, teriflunomide, and mitoxantrone. Data on circulating B-cell cytokine production are not available for natalizumab; thus, information on the relative concentrations of proinflammatory and anti-inflammatory cytokines in the circulation are not available for patients with MS treated with natalizumab. B-I indicates immature B cell; B-M, memory B cell; B-N, naive B cell; B-P, plasmablast; and CNS, central nervous system.

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The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
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