Anti-B cell therapies in multiple sclerosis

研究成果: Review article査読

抄録

Multiple sclerosis (MS) has long been considered a T-cell-mediated autoimmune disease of the central nervous system. However, newer evidence shows that B cells play a crucial role in the pathogenesis of MS via antibody production, antigen presentation, T cell stimulation and activation, and production of pro-inflammatory cytokines. Developing B cells express the CD20 molecule from the pre-B cell to the plasmablast stage, and the anti-CD20 monoclonal antibodies rituximab, ocrelizumab, ofatumumab and ublituximab are either in use or are being developed for treatment of MS as B cell-depleting therapies. They have shown profound efficacy in strongly suppressing relapse and radiological disease activity. Another promising approach is the inhibition of Bruton’s tyrosine kinase (BTK), a key enzyme that is intricately involved in signaling from the B cell antigen receptor and the Fc receptors in B cells and myeloid cells. BTK is considered to play an essential role for differentiation and survival of B-lineage cells, and BTK inhibition may dampen not only B cell activation but also innate immune activation in MS. Trials of BTK inhibitors are ongoing to establish their efficacy and safety in relapsing and progressive MS. The main safety issue with persistent B cell depletion is an increased risk of infection, possibly including an increased risk of severe COVID-19; unfortunately, vaccine responses against COVID-19 may also be blunted by anti-CD20 monoclonal antibodies.

本文言語English
ページ(範囲)228-237
ページ数10
ジャーナルClinical and Experimental Neuroimmunology
12
4
DOI
出版ステータスPublished - 2021 11月

ASJC Scopus subject areas

  • 神経科学(その他)
  • 免疫学
  • 免疫学および微生物学(その他)
  • 臨床神経学

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