Optimal response to dimethyl fumarate is mediated by a reduction of Th1-like Th17 cells after 3 months of treatment

María José Mansilla, Juan Navarro-Barriuso, Silvia Presas-Rodríguez, Aina Teniente-Serra, Bibiana Quirant-Sánchez, Cristina Ramo-Tello, Eva María Martínez-Cáceres

Research output: Contribution to journalArticleResearch

3 Citations (Scopus)

Abstract

© 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd. Aim: Dimethyl fumarate (DMF) is one of the most promising therapies for relapsing-remitting multiple sclerosis (RRMS) patients since it has shown immunomodulatory and neuroprotective effects. However, a percentage of RRMS patients do not exhibit an optimal response to DMF. The objective of this study was to identify early biomarkers of treatment response by analyzing changes in peripheral leukocyte subpopulations directly in whole blood samples. Methods: A longitudinal and prospective study analyzing peripheral blood leukocyte subpopulations in 22 RRMS patients before initiating DMF treatment (baseline) and at 1, 3, 6, and 12 months of follow-up was performed. Differences between no evidence of disease activity (NEDA) and ongoing disease activity (ODA) patients were analyzed. Results: The beneficial effect of DMF was associated with a specific depletion of memory CD4+ and CD8+ T lymphocytes and B cells. Importantly, only NEDA patients showed (a) a shift from a pro- to an antiinflammatory profile, with an increase of Th2 cells and a decrease of Th1-like Th17 lymphocytes; and (b) an increase of regulatory CD56bright NK cells. Conclusion: The optimal response to DMF is mediated by a shift to antiinflammatory and immunoregulatory profile, which puts forward Th1-like Th17 lymphocytes as a potential early biomarker of treatment response.
Original languageEnglish
Pages (from-to)995-1005
JournalCNS Neuroscience and Therapeutics
Volume25
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • biomarkers
  • dimethyl fumarate
  • immunomonitoring
  • multiple sclerosis
  • Th1-like Th17 lymphocytes

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