The Beneficial Clinical Effects of Teriflunomide in Experimental Autoimmune Myasthenia Gravis and the Investigation of the Possible Immunological Mechanisms.

Autor: Koseoglu E; Department of Biochemistry, Erciyes University School of Medicine, Kayseri, Turkey. emelk@erciyes.edu.tr.; Department of Neurology, Erciyes University School of Medicine, Kayseri, Turkey. emelk@erciyes.edu.tr., Sungur N; Department of Biochemistry, Erciyes University School of Medicine, Kayseri, Turkey., Muhtaroglu S; Department of Biochemistry, Erciyes University School of Medicine, Kayseri, Turkey., Zararsiz G; Department of Biostatistics, Erciyes University School of Medicine, Kayseri, Turkey.; Drug Application and Research Center (ERFARMA), Erciyes University, Kayseri, Turkey., Eken A; Department of Medical Biology, Erciyes University School of Medicine, Kayseri, Turkey.; Betul Ziya Eren Genome and Stem Cell Center, Kayseri, Turkey.
Jazyk: angličtina
Zdroj: Cellular and molecular neurobiology [Cell Mol Neurobiol] 2023 Jul; Vol. 43 (5), pp. 2071-2087. Date of Electronic Publication: 2022 Oct 11.
DOI: 10.1007/s10571-022-01286-5
Abstrakt: Myasthenia gravis (MG) is an autoantibody-mediated autoimmune disease characterized by skeletal muscle weakness exacerbated with exercise. There is a need for novel drugs effective in refractory MG. We aimed to test the potential of teriflunomide, an immunomodulatory drug currently used in rheumatoid arthritis and multiple sclerosis treatment, in a murine experimental autoimmune myasthenia gravis (EAMG) model. EAMG was induced by immunizations with recombinant acetylcholine receptor (AChR). Teriflunomide treatment (10 mg/kg/day, intraperitoneal) was initiated to one group of mice (n = 21) following the third immunization and continued for 5 weeks. The disease control group (n = 19) did not receive medication. Naïve mice (n = 10) received only mock immunization. In addition to the clinical scorings, the numbers of B cells and T cells, and cytokine profiles of T cells were examined by flow cytometry. Anti-AChR-specific antibodies in the peripheral blood serum were quantified by ELISA. Teriflunomide significantly reduced clinical disease scores and the absolute numbers of CD4+ T cells and some of their cytokine-producing subgroups (IFN-γ, IL 2, IL22, IL-17A, GM-CSF) in the spleen and the lymph nodes. The thymic CD4+ T cells were also significantly reduced. Teriflunomide mostly spared CD8+ T cells' numbers and cytokine production, while reducing CD138+CD19+lambda+ plasma B cells' absolute numbers and CD138 mean fluorescent intensities, probably decreasing the number of IgG secreting more mature plasma cells. It also led to some selective changes in the measurements of anti-AChR-specific antibodies in the serum. Our results showed that teriflunomide may be beneficial in the treatment of MG in humans.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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