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

• Published in: Cellular and molecular neurobiology 2023-07, Vol.43 (5), p.2071-2087
• Main Authors: Koseoglu, Emel, Sungur, Neslihan, Muhtaroglu, Sabahattin, Zararsiz, Gokmen, Eken, Ahmet
• Format: Article
• Language: English
• Subjects: Acetylcholine receptors; Autoantibodies; Autoimmune diseases; Biomedical and Life Sciences; Biomedicine; CD19 antigen; CD4 antigen; CD8 antigen; Cell Biology; Cytokines; Disease control; Enzyme-linked immunosorbent assay; Experimental autoimmune myasthenia gravis; Flow cytometry; Granulocyte-macrophage colony-stimulating factor; Immunization; Immunoglobulin G; Immunomodulation; Interleukin 22; Lymph nodes; Lymphocytes; Lymphocytes B; Lymphocytes T; Multiple sclerosis; Myasthenia gravis; Neurobiology; Neuromuscular junctions; Neurosciences; Original Research; Rheumatoid arthritis; Skeletal muscle; Thymus; γ-Interferon
• ISSN: 0272-4340; 1573-6830
• DOI: 10.1007/s10571-022-01286-5

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