Dimethyl fumarate treatment of relapsing-remitting multiple sclerosis influences B-cell subsets

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.