Optimal response to dimethyl fumarate is mediated by a reduction of Th1-like Th17 cells after 3 months of treatment
Mansilla Lopez, Maria Jose (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Navarro-Barriuso, Juan (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Presas-Rodríguez, Silvia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Teniente Serra, Aina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Quirant, Bibiana (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ramo-Tello, Cristina (Universitat Autònoma de Barcelona. Departament de Medicina)
Martínez Cáceres, Eva María (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)

Date:	2019
Abstract:	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. 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. 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 CD56 bright NK cells. 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.
Grants:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR103 Ministerio de Economía y Competitividad PI14/01175 European Commission BM0907 European Commission BM1305
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Biomarkers ; Dimethyl fumarate ; Immunomonitoring ; Multiple sclerosis ; Th1-like Th17 lymphocytes
Published in:	CNS neuroscience & therapeutics, Vol. 25 (2019) , p. 995-1005, ISSN 1755-5949

DOI: 10.1111/cns.13142
PMID: 31066225

11 p, 2.0 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles