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


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Koseoglu E., SUNGUR N., MUHTAROĞLU S., ZARARSIZ G., EKEN A.

Cellular and Molecular Neurobiology, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2022
  • Doi Number: 10.1007/s10571-022-01286-5
  • Journal Name: Cellular and Molecular Neurobiology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Keywords: Teriflunomide, Myasthenia gravis, Anti-acetylcholine receptor antibodies, Cytokines, Lymphocytes, ORAL TERIFLUNOMIDE, CELLS, AUTOANTIBODIES, COMPLEMENT, ANTIBODIES, SUBCLASS, MUSK
  • Kayseri University Affiliated: No

Abstract

© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.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. Graphical Abstract: [Figure not available: see fulltext.].