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Ann Clin Transl Neurol. 2019 Jan 15;6(2):355-363. doi: 10.1002/acn3.711. eCollection 2019 Feb.

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

Author information

1
Department of Immunology Hospital Universitario Ramón y Cajal IRYCIS Madrid Spain.
2
The Spanish Network of Multiple Sclerosis (REEM) Spain.
3
Department of Neurology Hospital Universitario Ramón y Cajal IRYCIS Madrid Spain.
4
Department of Neurology Hospital Clínico San Carlos IDISSC Madrid Spain.
5
Department of Neurology Hospital Universitario Quirónsalud Madrid Madrid Spain.

Abstract

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.

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