Monday, 19 October 2015

Dimethyl fumarate reduces white blood cell counts

Longbrake EE, Ramsbottom MJ, Cantoni C, Ghezzi L, Cross AH, Piccio L.Dimethyl fumarate selectively reduces memory T cells in multiple sclerosis patients. Mult Scler. 2015. pii: 1352458515608961. [Epub ahead of print]

BACKGROUND:Dimethyl fumarate (DMF) alters the phenotype of circulating immune cells and causes lymphopenia in a subpopulation of treatedmultiple 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.

So one mechanims that may contribute to the action of tecfidera is depletion of memonry T cells (and B cells). In excess this may contribute to the risk of PML also

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