Th1Th17 Lymphocyte Subpopulation as a Predictive Biomarker of Disease Activity in Multiple Sclerosis Patients under Dimethyl Fumarate or Fingolimod Treatment.

Bibiana Quirant-Sánchez, Silvia Presas-Rodriguez, María José Mansilla, Aina Teniente-Serra, José V Hervás-García, Luis Brieva, Ester Moral-Torres, Antonio Cano, Elvira Munteis, Juan Navarro-Barriuso, Eva M Martínez-Cáceres, Cristina Ramo-Tello
Author Information
  1. Bibiana Quirant-Sánchez: Immunology Division, LCMN, Hospital Universitari Germans Trias i Pujol and Research Institute, Campus Can Ruti, Badalona, Barcelona, Spain. ORCID
  2. Silvia Presas-Rodriguez: Multiple Sclerosis Unit, Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
  3. María José Mansilla: Immunology Division, LCMN, Hospital Universitari Germans Trias i Pujol and Research Institute, Campus Can Ruti, Badalona, Barcelona, Spain.
  4. Aina Teniente-Serra: Immunology Division, LCMN, Hospital Universitari Germans Trias i Pujol and Research Institute, Campus Can Ruti, Badalona, Barcelona, Spain.
  5. José V Hervás-García: Multiple Sclerosis Unit, Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
  6. Luis Brieva: Neurology Department of Hospital Arnau Vilanova, Lleida, Spain.
  7. Ester Moral-Torres: Neurology Department of Hospital San Joan Despi Moises Broggi, Barcelona, Spain.
  8. Antonio Cano: Neurology Department of Hospital de Mataró, Mataró, Barcelona, Spain.
  9. Elvira Munteis: Neurology Department of Hospital del Mar, Barcelona, Spain.
  10. Juan Navarro-Barriuso: Immunology Division, LCMN, Hospital Universitari Germans Trias i Pujol and Research Institute, Campus Can Ruti, Badalona, Barcelona, Spain.
  11. Eva M Martínez-Cáceres: Immunology Division, LCMN, Hospital Universitari Germans Trias i Pujol and Research Institute, Campus Can Ruti, Badalona, Barcelona, Spain. ORCID
  12. Cristina Ramo-Tello: Multiple Sclerosis Unit, Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain. ORCID

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 ( = 22) or fingolimod ( = 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%. nonrelapsed: 9.25 ± 3.17%, < 0.05) and Th1Th17 cells (relapsed: 15.65 ± 6.15%. nonrelapsed: 10.14 ± 4.05%, < 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 Th1Th17cells < 11.48% whose relapse-free survival was 88% ( = 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%. no MRI activity: 9.82 ± 4.06%, < 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.

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MeSH Term

Adult
Biomarkers
Dimethyl Fumarate
Female
Fingolimod Hydrochloride
Humans
Kaplan-Meier Estimate
Male
Multiple Sclerosis
T-Lymphocyte Subsets
Th17 Cells

Chemicals

Biomarkers
Dimethyl Fumarate
Fingolimod Hydrochloride

Word Cloud

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