Silvia Medina1, Noelia Villarrubia1, Susana Sainz de la Maza2, José Lifante1, Lucienne Costa-Frossard2, Ernesto Roldán1, Carmen Picón1, José C Álvarez-Cermeño3, Luisa M Villar1. 1. Servicio de Inmunología, Hospital Universitario Ramón y Cajal, Madrid, Spain; IRYCIS, Madrid, Spain; REEM, Barcelona, Spain. 2. Servicio de Neurología, Hospital Universitario Ramón y Cajal, Madrid, Spain; IRYCIS, Madrid, Spain; REEM, Barcelona, Spain. 3. Servicio de Neurologia, Hospital Universitario Ramon y Cajal, Madrid, Spain; IRYCIS, Madrid, Spain; REEM, Barcelona, Spain; Department of Medicine, University of Alcala, Madrid, Spain.
Abstract
BACKGROUND: The precise mechanism of action of dimethyl fumarate (DMF) treatment in MS remains unknown. OBJECTIVE: To identify the changes in the blood lymphocyte profile of MS patients predicting no evidence of disease activity (NEDA) status after DMF treatment. METHODS: We studied blood lymphocyte subsets of 64 MS patients treated with DMF at baseline and after 6 months of treatment by flow cytometry. NEDA (41 patients) or ongoing disease activity (ODA, 23 patients) were monitored after a year of follow-up. RESULTS: During treatment, all patients experienced an increase in the naive T cells and a decrease in effector memory ones. However, only NEDA patients showed a significant reduction in central memory CD4+ and CD8+ T cells, memory B cells, CD4+ T cells producing interferon (IFN)-gamma, CD8+ T cells producing tumor necrosis factor-alpha (TNF-alpha), and IFN-gamma and B cells producing TNF-alpha. Additionally, they had an increase in regulatory CD56bright cells not observed in ODA group. After treatment, there was a negative correlation between CD56bright cells and CD8+ T cells producing IFN-gamma and TNF-alpha. CONCLUSION: A pro-tolerogenic shift in the blood leukocyte profile associates with an optimal response to DMF in MS.
BACKGROUND: The precise mechanism of action of dimethyl fumarate (DMF) treatment in MS remains unknown. OBJECTIVE: To identify the changes in the blood lymphocyte profile of MS patients predicting no evidence of disease activity (NEDA) status after DMF treatment. METHODS: We studied blood lymphocyte subsets of 64 MS patients treated with DMF at baseline and after 6 months of treatment by flow cytometry. NEDA (41 patients) or ongoing disease activity (ODA, 23 patients) were monitored after a year of follow-up. RESULTS: During treatment, all patients experienced an increase in the naive T cells and a decrease in effector memory ones. However, only NEDApatients showed a significant reduction in central memory CD4+ and CD8+ T cells, memory B cells, CD4+ T cells producing interferon (IFN)-gamma, CD8+ T cells producing tumor necrosis factor-alpha (TNF-alpha), and IFN-gamma and B cells producing TNF-alpha. Additionally, they had an increase in regulatory CD56bright cells not observed in ODA group. After treatment, there was a negative correlation between CD56bright cells and CD8+ T cells producing IFN-gamma and TNF-alpha. CONCLUSION: A pro-tolerogenic shift in the blood leukocyte profile associates with an optimal response to DMF in MS.
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Authors: Carmen Picón; Amalia Tejeda-Velarde; José Ignacio Fernández-Velasco; Manuel Comabella; Roberto Álvarez-Lafuente; Ester Quintana; Susana Sainz de la Maza; Enric Monreal; Noelia Villarrubia; José Carlos Álvarez-Cermeño; María Inmaculada Domínguez-Mozo; Lluís Ramió-Torrentà; Eulalia Rodríguez-Martín; Ernesto Roldán; Yolanda Aladro; Silvia Medina; Mercedes Espiño; Jaime Masjuan; Clara Matute-Blanch; Marta Muñoz-San Martín; Carmen Espejo; Carmen Guaza; Alfonso Muriel; Lucienne Costa-Frossard; Luisa María Villar Journal: Front Immunol Date: 2021-07-12 Impact factor: 7.561