Th1Th17CM lymphocyte subpopulation as a predictive biomarker of disease activity in multiple sclerosis patients under dimethyl fumarate or fingolimod treatment
Quirant, Bibiana (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Presas-Rodriguez, Silvia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Mansilla Lopez, Maria Jose (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Teniente Serra, Aina (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Hervas-Garcia, Jose Vicente (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Brieva Ruiz, Luis (Hospital Arnau de Vilanova (Lleida, Catalunya))
Moral-Torres, Ester (Hospital de Sant Joan Despí Moisès Broggi)
Cano, Antonio (Hospital de Mataró. Consorci Sanitari del Maresme)
Munteis, Elvira (Hospital del Mar (Barcelona, Catalunya))
Navarro-Barriuso, Juan (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Martínez Cáceres, Eva María (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Ramo-Tello, Cristina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)

Date:	2019
Abstract:	Peripheral blood biomarkers able to predict disease activity in multiple sclerosis (MS) patients have not been identified yet. Here, we analyzed the immune phenotype of T lymphocyte subpopulations in peripheral blood samples from 66 RRMS patients under DMF (n = 22) or fingolimod (n = 44) treatment, by flow cytometry. A correlation study between the percentage and absolute cell number of each lymphocyte subpopulation with the presence of relapses or new MRI lesions during 12-month follow-up was performed. Patients who had undergone relapses showed at baseline higher percentage of Th1 cells (relapsed: 11 60 ± 4 17%vs. nonrelapsed: 9 25 ± 3 17%, p < 0 05) and Th1Th17 cells (relapsed: 15 65 ± 6 15%vs. nonrelapsed: 10 14 ± 4 05%, p < 0 01) before initiating DMF or fingolimod treatment. Kaplan-Meier analysis revealed that patients with Th1Th17 (CD4CCR7CD45RACCR6CXCR3) cells > 11 48% had a 50% relapse-free survival compared to patients with Th1Th17 cells < 11 48% whose relapse-free survival was 88% (p = 0 013, log-rank test). Additionally, a high percentage of Th1Th17 cells was also found in patients with MRI activity (MRI activity: 14 02 ± 5 87%vs. no MRI activity: 9 82 ± 4 06%, p < 0 01). Our results suggest that the percentage of Th1Th17 lymphocytes at baseline is a predictive biomarker of activity during the first 12 months of treatment, regardless of the treatment.
Grants:	Instituto de Salud Carlos III PI14/01175 Instituto de Salud Carlos III PI16/01737
Note:	This work has been supported by positive discussion through ENTIRE European network (BM0907; https://www.cost.eu/ actions/BM0907) and A FACTT network (COST Action BM1305: www.afactt.eu). COST is supported by the EU Framework Programme Horizon 2020. We thank Mr. Marco A. Fernández of the Cytometry Facility of IGTP for his continuous help and suggestions and Ms. Amanda Rus for her technical assistance. The authors are members of a consolidated group (02/2015-01/2018) as recognized by the Agency for Management of University and Research Grants (AGAUR) of the Generalitat of Catalonia. This study was sponsored in part by Novartis Pharmaceuticals Corporation and in part by the Spanish grants FIS PI14/01175 and PI16/01737, integrated in the Plan Nacional de I+D+I and cosupported by the ISCIII-Subdirección General de Evalua-ción and the Fondo Europeo de Desarrollo Regional (FEDER).
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
Published in:	Mediators of Inflammation, Vol. 2019 (2019) , art. 8147803, ISSN 1466-1861

DOI: 10.1155/2019/8147803
PMID: 31346315

10 p, 1.6 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