Dimethyl fumarate and Memory B cells

Longbrake EE, Cantoni C, Chahin S, Cignarella F, Cross AH, Piccio L. Dimethyl fumarate induces changes in B- and T-lymphocyte function independent of the effects on absolute lymphocyte count. Mult Scler. 2017:1352458517707069. doi: 10.1177/1352458517707069. [Epub ahead of print]

BACKGROUND:Dimethyl fumarate (DMF) is used to treat relapsing multiple sclerosis and causes lymphopenia in a subpopulation of treated individuals. Much remains to be learned about how the drug affects B- and T-lymphocytes.
OBJECTIVES:To characterize changes in B- and T-cell phenotype and function induced by DMF and to investigate whether low absolute lymphocyte count (ALC) is associated with unique functional changes.
METHODS:Peripheral blood mononuclear cells (PBMCs) were collected from DMF-treated patients, untreated patients, and healthy controls. A subset of DMF-treated patients was lymphopenic (ALC < 800). Multiparametric flow cytometry was used to evaluate cellular phenotypes. Functional response to non-specific and viral peptide stimulation was assessed.
RESULTS: DMF reduced circulating memory B-cells regardless of ALC. Follicular T-helper cells (CD4+ CXCR5+) and mucosal invariant T-cells (CD8+ CD161+) were also reduced. DMF reduced T-cell production of pro-inflammatory cytokines in response to polyclonal (PMA/ionomycin) and viral peptide stimulation, regardless of ALC. No differences in activation-induced cell death or circulating progenitors were observed between lymphopenic and non-lymphopenic DMF-treated patients.
CONCLUSION:These data implicate DMF-induced changes in lymphocytes as an important component of the drug’s efficacy and expand our understanding of the functional significance of DMF-induced lymphopenia.

As we have been saying effective drugs deplete memory B cells

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  • I'm on DMF and would like to know my lymphocyte subset levels. Would it cost more to the NHS to get this info when I have blood tests every 3 months?

    • The question is which subsets you do? and why do you do it?, Some are more bog standard, the CD4, CD8 and CD19 may be relatively easy but to get memory cells is a more complex stain, we can get this done at extra cost as the NHS has developed the assay. Some may not.

      Would it cost more to the NHS?, it depends on the value of the analysis, if it can predict disease activity, then it may influence the frequency of treatment say with ocrelizumab, but on DMF you are having it daily, can blood levels predict disease activity?

      At the AAN2017, Biogen did a wonderful study of immune subsets over time, if they could link that study to disease activity, we have the answer. Hopefully the study was not too short to pick that up. I ask ProfG to ask Biogen if there is follow-up. I have no answer so ither Biogen or profG are not on the case yet.

  • Yay! More evidence 🙂 clicked on link but couldn't see anymore. Hope you saw some data MD? Biogen study sounds interesting, have been thinking I'd love to have a record of my memB cell count.

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