title: Dimethyl fumarate selectively reduces memory T cells in multiple sclerosis patients.
abstract: Dimethyl fumarate (DMF) alters the phenotype of circulating immune cells and causes lymphopenia in a subpopulation of treated multiple sclerosis (MS) patients.
  
  
  
  To phenotypically characterize circulating leukocytes in DMF-treated MS patients.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, Missouri.
authors.forename: E E
authors.initials: EE
authors.lastname: Longbrake
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, Missouri.
authors.forename: M J
authors.initials: MJ
authors.lastname: Ramsbottom
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, Missouri.
authors.forename: C
authors.initials: C
authors.lastname: Cantoni
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, Missouri.|Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Ghezzi
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, Missouri.
authors.forename: A H
authors.initials: AH
authors.lastname: Cross
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, Missouri.
authors.forename: L
authors.initials: L
authors.lastname: Piccio
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D000069462:Dimethyl Fumarate / Q000009:adverse effects / Q000627:therapeutic use*; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects*; D016130:Immunophenotyping / Q000379:methods; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000139:chemically induced / Q000276:immunology; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D000069462:Dimethyl Fumarate
keywords: Dimethyl fumarate; immunocompetence; immunology; lymphocyte types; lymphopenia; memory T cells; multiple sclerosis; neuroimmunology; relapse