Th1Th17CM lymphocyte subpopulation as a predictive biomarker of disease activity in multiple sclerosis patients under dimethyl fumarate or fingolimod treatment

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 Th1Th17CM cells < 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.