Dimethyl fumarate selectively reduces memory T cells in multiple sclerosis patients

Erin E. Longbrake, Michael J. Ramsbottom, Claudia Cantoni, Laura Ghezzi, Anne H. Cross, Laura Piccio

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Dimethyl fumarate (DMF) alters the phenotype of circulating immune cells and causes lymphopenia in a subpopulation of treated multiple sclerosis (MS) patients. Objective: To phenotypically characterize circulating leukocytes in DMF-treated MS patients. Methods: Cross-sectional observational comparisons of peripheral blood from DMF-treated MS patients (n = 17 lymphopenic and n = 24 non-lymphopenic), untreated MS patients (n = 17) and healthy controls (n = 23); immunophenotyped using flow cytometry. Longitudinal samples were analyzed for 13 DMF-treated patients. Results: Lymphopenic DMF-treated patients had significantly fewer circulating CD8+ and CD4+ T cells, CD56dim natural killer (NK) cells, CD19+ B cells and plasmacytoid dendritic cells when compared to controls. CXCR3+ and CCR6+ expression was disproportionately reduced among CD4+ T cells, while the proportion of T-regulatory (T-reg) cells was unchanged. DMF did not affect circulating CD56hi NKcells, monocytes or myeloid dendritic cells. Whether lymphopenic or not, DMF-treated patients had a lower proportion of circulating central and effector memory T cells and concomitant expansion of naïve T cells compared to the controls. Conclusions: DMF shifts the immunophenotypes of circulating T cells, causing a reduction of memory cells and a relative expansion of naïve cells, regardless of the absolute lymphocyte count. This may represent one mechanism of action of the drug. Lymphopenic patients had a disproportionate loss of CD8+ T-cells, which may affect their immunocompetence.

Original languageEnglish
Pages (from-to)1061-1070
Number of pages10
JournalMultiple Sclerosis
Volume22
Issue number8
DOIs
Publication statusPublished - Jul 1 2016

Keywords

  • Dimethyl fumarate
  • immunocompetence
  • immunology
  • lymphocyte types
  • lymphopenia
  • memory T cells
  • multiple sclerosis
  • neuroimmunology
  • relapse

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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