Focused on the Effect of Teriflunomide on Lymphocyte Subpopulations
Teriflunomide is a common choice for long-term therapy of the relapsing-remitting form of multiple sclerosis. The use of this immunomodulatory agent results in a decrease in lymphocyte numbers. Its effect on different lymphocyte subpopulations, however, has not been fully elucidated. Italian authors of a study published in the journal Neurology: Neuroimmunology and Neuroinflammation attempted to refine this knowledge.
Mechanism of Action
Teriflunomide is an immunomodulatory agent with anti-inflammatory effects that selectively and reversibly inhibits the mitochondrial enzyme dihydroorotate dehydrogenase necessary for de novo pyrimidine synthesis. Teriflunomide thus reduces the proliferation of activated B and T lymphocytes that require de novo pyrimidine synthesis for growth. The exact mechanism underlying the therapeutic effect of teriflunomide in multiple sclerosis is not fully known but is based on the reduction in the number of lymphocytes.
Study Methodology and Course
The study included 10 patients with relapsing-remitting multiple sclerosis over the age of 18. During the study, none of the observed patients experienced a relapse. Blood samples were analyzed before 3-month or 12-month teriflunomide treatment and after.
In the 3-month treated group, there were 3 patients (2 men and 1 woman), their average age was 43.6 ± 1.5 years, the average EDSS score was 3.0 ± 1.5, and the average disease duration of multiple sclerosis was 15.3 ± 10.5 years. In the 12-month treated group, there were 7 female patients, their average age was 54.8 ± 8.9 years; the average EDSS score was 3.0 ± 1.5 before treatment and 3.1 ± 1.7 after 12 months, and the average disease duration was 13.4 ± 4.8 years.
Subpopulations of B lymphocytes (memory cells, regulatory and mature), T lymphocytes (effector and regulatory), and NK cells (CD56 dim and CD56 bright) were analyzed by flow cytometry.
Results and Conclusion
Teriflunomide significantly reduced the absolute numbers of CD19+ B lymphocytes, regulatory and mature B lymphocytes. T lymphocytes were affected to a lesser extent. The numbers of both effector CD4+ T lymphocytes (TH1, TH17, and TH1/17) and regulatory CD8+ and CD4+ T lymphocytes decreased. No detectable decrease in NK cells was observed.
These data indicate that teriflunomide affects those immune system cells that play a crucial role in the immunopathogenesis of multiple sclerosis, particularly B lymphocytes (CD19, regulatory and mature), and to a lesser extent T lymphocytes.
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Source: Gandoglia I., Ivaldi F., Laroni A. et al. Teriflunomide treatment reduces B cells in patients with MS. Neurol Neuroimmunol Neuroinflamm 2017; 4 (6): e403, doi: 10.1212/NXI.0000000000000403.
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