title: Dimethyl fumarate treatment of relapsing-remitting multiple sclerosis influences B-cell subsets.
abstract: OBJECTIVE
  To test the hypothesis that dimethyl fumarate (Tecfidera, BG-12) affects B-cell subsets in patients with relapsing-remitting multiple sclerosis (RRMS).
  
  
  METHODS
  Peripheral blood B cells were compared for surface marker expression in patients with RRMS prior to initiation of treatment, after 4-6 months, and at more than 1 year of treatment with BG-12. Production of interleukin (IL)-10 by RRMS patient B cells was also analyzed.
  
  
  RESULTS
  Total numbers of peripheral blood B lymphocytes declined after 4-6 months of BG-12 treatment, due to losses in both the CD27+ memory B cells and CD27(neg) B-cell subsets. Some interpatient variability was observed. In contrast, circulating CD24(high)CD38(high) (T2-MZP) B cells increased in percentage in the majority of patients with RRMS after 4-6 months and were present in higher numbers in all of the patients after 12 months of treatment. The CD43+CD27+ B-1 B cells also increased at the later time point in most patients but were unchanged at 4-6 months compared to pretreatment levels. Purified B cells from 7 of the 9 patients with RRMS tested after 4-6 months of treatment were able to produce IL-10 following CD40 ligand stimulation, and the amount corresponded with the combined levels of T2-MZP and B-1 B cells in the sample. None of the patients with RRMS in this study have had a relapse while taking BG-12.
  
  
  CONCLUSIONS
  These data suggest that BG-12 differentially affects B-cell subsets in patients with RRMS, resulting in increased numbers of circulating B lymphocytes with regulatory capacity.
authors.affiliation: Department of Internal Medicine, Division of Rheumatology (S.K.L.), Graduate Program in Immunology, Program in Biomedical Sciences (S.K.L., S.H.T., Y.M.-D.), and Department of Neurology (Q. Wu, Q. Wang, C.A.D., G.M., Y.M.-D.), University of Michigan Medical School, Ann Arbor.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Lundy
authors.affiliation: Department of Internal Medicine, Division of Rheumatology (S.K.L.), Graduate Program in Immunology, Program in Biomedical Sciences (S.K.L., S.H.T., Y.M.-D.), and Department of Neurology (Q. Wu, Q. Wang, C.A.D., G.M., Y.M.-D.), University of Michigan Medical School, Ann Arbor.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, Division of Rheumatology (S.K.L.), Graduate Program in Immunology, Program in Biomedical Sciences (S.K.L., S.H.T., Y.M.-D.), and Department of Neurology (Q. Wu, Q. Wang, C.A.D., G.M., Y.M.-D.), University of Michigan Medical School, Ann Arbor.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Division of Rheumatology (S.K.L.), Graduate Program in Immunology, Program in Biomedical Sciences (S.K.L., S.H.T., Y.M.-D.), and Department of Neurology (Q. Wu, Q. Wang, C.A.D., G.M., Y.M.-D.), University of Michigan Medical School, Ann Arbor.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Dowling
authors.affiliation: Department of Internal Medicine, Division of Rheumatology (S.K.L.), Graduate Program in Immunology, Program in Biomedical Sciences (S.K.L., S.H.T., Y.M.-D.), and Department of Neurology (Q. Wu, Q. Wang, C.A.D., G.M., Y.M.-D.), University of Michigan Medical School, Ann Arbor.
authors.forename: Sophina H
authors.initials: SH
authors.lastname: Taitano
authors.affiliation: Department of Internal Medicine, Division of Rheumatology (S.K.L.), Graduate Program in Immunology, Program in Biomedical Sciences (S.K.L., S.H.T., Y.M.-D.), and Department of Neurology (Q. Wu, Q. Wang, C.A.D., G.M., Y.M.-D.), University of Michigan Medical School, Ann Arbor.
authors.forename: Guangmei
authors.initials: G
authors.lastname: Mao
authors.affiliation: Department of Internal Medicine, Division of Rheumatology (S.K.L.), Graduate Program in Immunology, Program in Biomedical Sciences (S.K.L., S.H.T., Y.M.-D.), and Department of Neurology (Q. Wu, Q. Wang, C.A.D., G.M., Y.M.-D.), University of Michigan Medical School, Ann Arbor.
authors.forename: Yang
authors.initials: Y
authors.lastname: Mao-Draayer