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.
Dimethyl fumarate selectively reduces memory T cells in multiple sclerosis patients / E.E. Longbrake, M.J. Ramsbottom, C. Cantoni, L. Ghezzi, A.H. Cross, L. Piccio. - In: MULTIPLE SCLEROSIS. - ISSN 1352-4585. - 22:8(2016), pp. 1061-1070.
Dimethyl fumarate selectively reduces memory T cells in multiple sclerosis patients
C. Cantoni;L. Ghezzi;L. Piccio
2016
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.File | Dimensione | Formato | |
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