Objective: To elucidate the immunomodulatory effects of dimethyl fumarate (DMF) on B cells in patients with relapsing MS receiving DMF as a "1st-line" vs "2nd-line" therapy.
Methods: B cells were isolated from 43 patients with MS at baseline and after 15-week DMF therapy. Phenotype and functional markers and cytokine profile were assessed by flow cytometry. Analysis included clinical and MRI parameters recorded during a 1-year follow-up
Results: 1st-line and 2nd-line patients presented several differences in their baseline immune profile, which corresponded with differences in their immunologic response to DMF treatment. DMF reduced the proportions of B cells and CD8 T cells whereas increased monocytes. DMF reduced memory B cells, including plasma cells in 2nd-line patients only, whereas strongly increased transitional B cells. Several IL10 B-cell subsets and TGFβ B cells were increased. Proinflammatory LTα and TNFα B cells were reduced, while IL4 B cells elevated, whereas IFNγ B cells showed opposite effects in 1st-line and 2nd-line patients. HLA and ICAM-1 expression was increased, but % CD86 B cells reduced. The expression of B-cell activating factor receptor and the proportion of activated CD69 B cells were increased.
Conclusions: DMF is associated with increased transitional and IL10 and TGFβ regulatory B cells and a shift toward a more anti-inflammatory immune profile. Cell activation with reduced costimulatory capacity may induce immune hyporesponsiveness. Carryover effects of preceding therapies in 2nd-line patients and the stage of disease influence the immune profile of the patients and the immunomodulatory effects of DMF.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192691 | PMC |
| http://dx.doi.org/10.1212/NXI.0000000000000508 | DOI Listing |
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