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- Title
Dimethyl fumarate selectively reduces memory T cells in multiple sclerosis patients.
- Authors
Longbrake, Erin E.; Ramsbottom, Michael J.; Cantoni, Claudia; Ghezzi, Laura; Cross, Anne H.; Piccio, Laura
- 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.
- Subjects
MULTIPLE sclerosis; PHENOTYPES; LYMPHOPENIA; T cells; MONOCYTES; IMMUNOCOMPETENT cells; LEUCOCYTES; PATIENTS
- Publication
Multiple Sclerosis Journal, 2016, Vol 22, Issue 8, p1061
- ISSN
1352-4585
- Publication type
Article
- DOI
10.1177/1352458515608961