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Dimethyl fumarate selectively reduces memory T cells in multiple sclerosis patients

2015; SAGE Publishing; Volume: 22; Issue: 8 Linguagem: Inglês

10.1177/1352458515608961

1477-0970

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

T-cell and B-cell Immunology

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, CD56 dim 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 CD56 hi 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.