Dimethyl fumarate selectively reduces memory T cells in multiple sclerosis patients

作者：Longbrake Erin E^*; Ram**ottom Michael J; Cantoni Claudia; Ghezzi Laura; Cross Anne H; Piccio Laura

来源：Multiple Sclerosis, 2016, 22(8): 1061-1070.

DOI：10.1177/1352458515608961

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

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.

• 出版日期2016-7