Dimethyl fumarate induces changes in B- and T-lymphocyte function independent of the effects on absolute lymphocyte count

Erin E. Longbrake, Claudia Cantoni, Salim Chahin, Francesca Cignarella, Anne H. Cross, Laura Piccio

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Background: Dimethyl fumarate (DMF) is used to treat relapsing multiple sclerosis and causes lymphopenia in a subpopulation of treated individuals. Much remains to be learned about how the drug affects B- and T-lymphocytes. Objectives: To characterize changes in B- and T-cell phenotype and function induced by DMF and to investigate whether low absolute lymphocyte count (ALC) is associated with unique functional changes. Methods: Peripheral blood mononuclear cells (PBMCs) were collected from DMF-treated patients, untreated patients, and healthy controls. A subset of DMF-treated patients was lymphopenic (ALC < 800). Multiparametric flow cytometry was used to evaluate cellular phenotypes. Functional response to non-specific and viral peptide stimulation was assessed. Results: DMF reduced circulating memory B-cells regardless of ALC. Follicular T-helper cells (CD4+ CXCR5+) and mucosal invariant T-cells (CD8+ CD161+) were also reduced. DMF reduced T-cell production of pro-inflammatory cytokines in response to polyclonal (PMA/ionomycin) and viral peptide stimulation, regardless of ALC. No differences in activation-induced cell death or circulating progenitors were observed between lymphopenic and non-lymphopenic DMF-treated patients. Conclusion: These data implicate DMF-induced changes in lymphocytes as an important component of the drug’s efficacy and expand our understanding of the functional significance of DMF-induced lymphopenia.

Original languageEnglish
Pages (from-to)728-738
Number of pages11
JournalMultiple Sclerosis Journal
Volume24
Issue number6
DOIs
StatePublished - May 1 2018

Keywords

  • Dimethyl fumarate
  • disease-modifying therapy
  • immunology
  • multiple sclerosis

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