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The Beneficial Clinical Effects of Teriflunomide in Experimental Autoimmune Myasthenia Gravis and the Investigation of the Possible Immunological Mechanisms.
Koseoglu, Emel; Sungur, Neslihan; Muhtaroglu, Sabahattin; Zararsiz, Gokmen; Eken, Ahmet.
Afiliación
  • Koseoglu E; Department of Biochemistry, Erciyes University School of Medicine, Kayseri, Turkey. emelk@erciyes.edu.tr.
  • Sungur N; Department of Neurology, Erciyes University School of Medicine, Kayseri, Turkey. emelk@erciyes.edu.tr.
  • Muhtaroglu S; Department of Biochemistry, Erciyes University School of Medicine, Kayseri, Turkey.
  • Zararsiz G; Department of Biochemistry, Erciyes University School of Medicine, Kayseri, Turkey.
  • Eken A; Department of Biostatistics, Erciyes University School of Medicine, Kayseri, Turkey.
Cell Mol Neurobiol ; 43(5): 2071-2087, 2023 Jul.
Article en En | MEDLINE | ID: mdl-36219379
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Miastenia Gravis Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Mol Neurobiol Año: 2023 Tipo del documento: Article País de afiliación: Turquía Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Miastenia Gravis Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Mol Neurobiol Año: 2023 Tipo del documento: Article País de afiliación: Turquía Pais de publicación: Estados Unidos