Dimethyl fumarate selectively reduces memory T cells in multiple sclerosis patients.

Document Type

Article

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, 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.

Keywords

CD8-Positive T-Lymphocytes, Case-Control Studies, Cross-Sectional Studies, Dimethyl Fumarate, Flow Cytometry, Humans, Immunologic Memory, Immunophenotyping, Immunosuppressive Agents, Lymphocyte Count, Lymphopenia, Multiple Sclerosis, Phenotype, T-Lymphocytes, Regulatory, Time Factors, Treatment Outcome

Medical Subject Headings

CD8-Positive T-Lymphocytes; Case-Control Studies; Cross-Sectional Studies; Dimethyl Fumarate; Flow Cytometry; Humans; Immunologic Memory; Immunophenotyping; Immunosuppressive Agents; Lymphocyte Count; Lymphopenia; Multiple Sclerosis; Phenotype; T-Lymphocytes, Regulatory; Time Factors; Treatment Outcome

Publication Date

7-1-2016

Publication Title

Multiple sclerosis (Houndmills, Basingstoke, England)

ISSN

1477-0970

Volume

22

Issue

8

First Page

1061

Last Page

1070

PubMed ID

26459150

Digital Object Identifier (DOI)

10.1177/1352458515608961

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