Teriflunomide induces a tolerogenic bias in blood immune cells of MS patients

OBJECTIVES: Teriflunomide, a disease‐modifying treatment approved for multiple sclerosis (MS), inhibits reversibly dihydroorotate dehydrogenase, an enzyme involved in de novo pyrimidine biosynthesis and down‐regulates proliferation of activated lymphocytes. We aimed to study the impact of this drug in the lymphocyte profiles of MS patients. METHODS: Fifty‐five patients with relapsing‐remitting MS who initiated teriflunomide treatment were included in the study. We studied peripheral blood mononuclear cells obtained before and 6 months after treatment initiation and explored effector, memory, and regulatory cells by flow cytometry. Wilcoxon matched pair tests were used to assess differences between basal and 6 months after treatment results. P‐values were corrected with Bonferroni test. RESULTS: When explored T and B cell subsets, we observed a decrease in the percentages of terminally differentiated CD4+ T cells (P = 0.001) and plasmablasts (P < 0.0001) after 6 months of treatment. These results were confirmed with the total cell number. When studied immunomodulatory cells, we observed a clear increase of monocytes expressing programmed death‐ligand 1 (PD‐L1) (P = 0.005), which correlated negatively with all effector CD8+ T cell subsets. We also observed an increase in the percentage of CD8+ T cells (P = 0.028) and monocytes (P = 0.04) producing IL‐10. CONCLUSIONS: Teriflunomide induces a specific reduction in effector T and B cells that have shown to play a role in MS course and an increase in immunomodulatory cells. Particularly, this drug induces the expression of PD‐L1, a molecule involved in tolerance to autoantigens, which can contribute to inhibit the abnormal immune response taking place in MS.