Th1Th17CM Lymphocyte Subpopulation as a Predictive Biomarker of Disease Activity in Multiple Sclerosis Patients under Dimethyl Fumarate or Fingolimod Treatment.

Bibiana Quirant-Sánchez,Luis Brieva,María José Mansilla,Antonio Cano,Juan Navarro-Barriuso,José V Hervás-García,Eva M Martínez-Cáceres,Cristina Ramo-Tello,Aina Teniente-Serra,Ester Moral-Torres,Silvia Presas-Rodriguez,Elvira Munteis

doi:10.1155/2019/8147803

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 Th1CM cells (relapsed: 11.60 ± 4.17%vs. nonrelapsed: 9.25 ± 3.17%, p < 0.05) and Th1Th17CM 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 Th1Th17CM (CD4+CCR7+CD45RA−CCR6+CXCR3+) cells > 11.48% had a 50% relapse-free survival compared to patients with Th1Th17CMcells < 11.48% whose relapse-free survival was 88% (p = 0.013, log-rank test). Additionally, a high percentage of Th1Th17CM 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 Th1Th17CM lymphocytes at baseline is a predictive biomarker of activity during the first 12 months of treatment, regardless of the treatment.

Highlights

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS), characterized by immune cell infiltration, demyelination, axonal degeneration, and astrogliosis [1, 2].The CD4+ T-helper (Th) lymphocytes are the most studied cell subpopulation in MS
These results were confirmed in vivo, by immunohistofluorescence studies of the CNS lesions of mice with EAE, indicating that Th1Th17 cells are more pathogenic than T-helper 1 (Th1) lymphocytes, both Th1 and T-helper 17 (Th17) are required for EAE induction [5]
Th1Th17CM cells in clinically active MS patients, we studied the association of MRI activity with this lymphocyte subpopulation

Summary

Introduction

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS), characterized by immune cell infiltration, demyelination, axonal degeneration, and astrogliosis [1, 2].The CD4+ T-helper (Th) lymphocytes are the most studied cell subpopulation in MS. Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS), characterized by immune cell infiltration, demyelination, axonal degeneration, and astrogliosis [1, 2]. In vitro studies showed that human Th1Th17 lymphocytes with memory phenotype (CD4+CD45RO+IL-17A+) migrate more avidly across the blood-brain barrier than Th1 cells [4]. These results were confirmed in vivo, by immunohistofluorescence studies of the CNS lesions of mice with EAE, indicating that Th1Th17 cells are more pathogenic than Th1 lymphocytes, both Th1 and Th17 are required for EAE induction [5]

Methods

Results

Conclusion