TY - JOUR
T1 - Optimal response to dimethyl fumarate is mediated by a reduction of Th1-like Th17 cells after 3 months of treatment
AU - Mansilla, María José
AU - Navarro-Barriuso, Juan
AU - Presas-Rodríguez, Silvia
AU - Teniente-Serra, Aina
AU - Quirant-Sánchez, Bibiana
AU - Ramo-Tello, Cristina
AU - Martínez-Cáceres, Eva María
N1 - © 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.
PY - 2019/9
Y1 - 2019/9
N2 - © 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.
AB - © 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.
KW - Th1-like Th17 lymphocytes
KW - biomarkers
KW - dimethyl fumarate
KW - immunomonitoring
KW - multiple sclerosis
UR - http://www.mendeley.com/research/optimal-response-dimethyl-fumarate-mediated-reduction-th1like-th17-cells-after-3months-treatment
U2 - 10.1111/cns.13142
DO - 10.1111/cns.13142
M3 - Article
C2 - 31066225
SN - 1755-5930
VL - 25
SP - 995
EP - 1005
JO - CNS Neuroscience and Therapeutics
JF - CNS Neuroscience and Therapeutics
IS - 9
ER -