期刊
MULTIPLE SCLEROSIS JOURNAL
卷 22, 期 8, 页码 1061-1070出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/1352458515608961
关键词
Dimethyl fumarate; immunocompetence; immunology; lymphocyte types; lymphopenia; memory T cells; multiple sclerosis; neuroimmunology; relapse
资金
- National MS Society [JF 2144A2/1]
- US National Institutes of Health (NIH) [UL1 TR000448]
- Barnes-Jewish Hospital Foundation (The Manny and Rosalyn Rosenthal, John L Trotter MS Center Chair in Neuroimmunology)
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 naive 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 naive 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.
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