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February 2016

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

Author Affiliations
  • 1Department of Neurology, Washington University, St Louis, Missouri
JAMA Neurol. 2016;73(2):219-225. doi:10.1001/jamaneurol.2015.3977

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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