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Communication Dans Un Congrès Année : 2021

Monoclonal antibody anti -IL-23 ameliorates neuromuscular defects in Myasthenia Gravis mouse model

Résumé

Autoimmune myasthenia gravis (MG) is a rare neuromuscular disease due to auto-antibodies directed against acetylcholine receptors (AChRs) located at the neuromuscular junction. The induced neuromuscular junction (NMJ) dysfunctions lead to muscle weakness and fatigue. Previous data showed that pathogenic Th-17 cells are increased in sera of AChR+ MG patients. Therefore, we aimed to study the effect of a monoclonal anti-IL-23 antibody that targets pathogenic Th17 cells, in the classical experimental MG mouse model (EAMG). EAMG is based on active immunization of C57BL6 mice with torpedo fish-AChR. This model allows us to determine the impact of anti-IL-23 treatment on EAMG clinical score and the production of anti- AChR antibodies. We observed that the anti-IL-23 treatment significantly ameliorated muscular EAMG clinical score. In addition, analysis by electromyography of muscle single fibers, in the tibialis anterior, showed that the treatment improved the transduction signal at the neuromuscular junction. Hence, myasthenic mice receiving the anti-IL-23 treatment did not displayed the typical MG decrement following repetitive fiber stimulations illustrating an improvement in the neuromuscular transmission. At a molecular level, the anti-IL-23 antibody stimulated gene expression of factors involved in muscle regeneration, and reduced the IL-17 related inflammation in the tibialis anterior. Finally, we observed a significant decreased production of the IgG2b antibody induced by the treatment. Together, these data suggest that targeted IL-23 therapy may induce significant clinical amelioration in EAMG due to potential concomitant beneficial effects on the autoantibody production and on the skeletal muscle functional defects
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Dates et versions

hal-03844130 , version 1 (15-11-2022)

Identifiants

  • HAL Id : hal-03844130 , version 1

Citer

Jose Adolfo Villegas, Sonia Berrih-Aknin, Rozen Le Panse, Nadine Dragin. Monoclonal antibody anti -IL-23 ameliorates neuromuscular defects in Myasthenia Gravis mouse model. 15th ISNI ( International Society of Neuroimmunology ) Congress, Nov 2021, virtual, France. ⟨hal-03844130⟩
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