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      Dimethyl fumarate selectively reduces memory T cells in multiple sclerosis patients

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          Abstract

          Background

          Dimethyl fumarate (DMF) alters the phenotype of circulating immune cells and causes lymphopenia in a subpopulation of treated 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, 24 non-lymphopenic), untreated MS patients (n=17) and healthy controls (n=23) that was 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 NK cells, CD19 + B-cells and plasmacytoid dendritic cells compared to controls. CXCR3 + and CCR6 + expression was disproportionately reduced among CD4 + T-cells while the proportion of T regulatory cells was unchanged. DMF did not affect circulating CD56 hi NK-cells, 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 controls.

          Conclusions

          DMF shifts the immunophenotypes of circulating T cells, causing reduction of memory cells and relative expansion of naïve cells regardless of absolute lymphocyte count. This may represent one mechanism of action of the drug. Lymphopenic patients had disproportionate loss of CD8 + T cells, which may affect their immunocompetence.

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          Author and article information

          Journal
          9509185
          20508
          Mult Scler
          Mult. Scler.
          Multiple sclerosis (Houndmills, Basingstoke, England)
          1352-4585
          1477-0970
          13 September 2015
          12 October 2015
          July 2016
          01 July 2017
          : 22
          : 8
          : 1061-1070
          Affiliations
          [1 ]Department of Neurology, Washington University in St. Louis, St. Louis, Missouri
          [2 ]Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy
          Author notes
          Corresponding Author: Erin Longbrake Address: 660 S. Euclid Box 8111, St. Louis, MO 63110, Phone: 314-362-3293, Fax: 314-747-1345, longbrakee@ 123456neuro.wustl.edu
          Article
          PMC4829494 PMC4829494 4829494 nihpa722077
          10.1177/1352458515608961
          4829494
          26459150
          137b3d27-27a0-449c-a2ad-889c8d36a0d8
          History
          Categories
          Article

          neuroimmunology,Dimethyl fumarate,multiple sclerosis,immunology

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