Myasthenia Gravis: etiology, pathophysiological & therapeutic approaches
Myasthenia gravis is an autoimmune diseases; diseases that affect more than 5% of the population. These are multifactorial diseases involving genetic predispositions, hormonal implication, dysfunctions of the immune system, and are triggered by unidentified factors. Myasthenia gravis is due to autoantibodies directed against components of the neuromuscular junction, mainly the acetylcholine receptor (AChR, 85% of cases) but sometimes also against the muscle-specific tyrosine kinase receptor (MuSK) or the LRP4 protein interacting with agrin. These autoantibodies reduce the efficiency of neuromuscular transmission and lead to abnormal muscle fatigability.
The thymus is most likely the site of initiation of myasthenia gravis with anti-AChR antibodies. Histological abnormalities of the thymus are very common: 50-60% of the patients present follicular hyperplasia with ectopic germinal centers, and 10-15% of the patient present a tumor of the thymus (Thymoma). Thymectomy is one of the treatments proposed to these patients.
The research projects developed by the team aim to understand the etiological and pathophysiological mechanisms involved in myasthenia gravis and to propose new therapeutic approaches. More specifically, our objectives are to:
- Elucidate the etiological mechanisms involved in autoimmunity by analyzing the impact of sex hormones and endocrine disruptors in central tolerance processes.
- Understand the cellular and molecular mechanisms at the origin of thymus inflammation and remodeling observed in patients.
- Study the immunoregulatory defects in myasthenia gravis patients by studying the functional phenotype of peripheral and thymic cells by mass cytometry (CyTOF).
- Develop new therapeutic approaches. In this context, we are studying the immunomodulatory and therapeutic potential of mesenchymal stem cells, and the potential of molecules interfering with inflammatory pathways.
- Search for circulating biomarkers to follow the evolution of the disease and the response to treatments.
| Name | Position | ORCID |
|---|
- Maartje Huijbers, Alexander Marx, Jaap Plomp, Rozen Le Panse, William Phillips. Advances in the understanding of disease mechanisms of autoimmune neuromuscular junction disorders. The Lancet Neurology, 2022, 21 (2), pp.163-175. ⟨10.1016/S1474-4422(21)00357-4⟩. ⟨hal-03563023⟩
- Halliez Marius, Cottin Steve, You Axel, Lemaitre Mégane, Ezan Jérome, et al.. MUSK CYSTEIN RICH DOMAIN IN AUTOIMMUNE MYASTHENIC SYNDROME. 14th MGFA International Conference On Myasthenia And Related Disorders, 2022, Miami (Florida), United States. ⟨hal-04002779⟩
- Frédérique Truffault, Axel You, Julien Verdier, Sophie Demeret, Rozen Le Panse, et al.. Decrease in non-classical monocytes in Myasthenia Gravis patients. Congrès annuel de la Société Française d’Immunologie, 2022, Nice, France. ⟨hal-03861651⟩
- Konstantinos Savvatis, Christoffer Rasmus Vissing, Lori Klouvi, Anca Rezeda Florian, Mehjabin Rahman, et al.. Cardiac Outcomes in Adults With Mitochondrial Diseases. Journal of the American College of Cardiology, 2022, 80 (15), pp.1421-1430. ⟨10.1016/j.jacc.2022.08.716⟩. ⟨hal-03837169⟩
- Halliez Marius, Cottin Steve, You Axel, Lemaitre Mégane, Ezan Jérome, et al.. MUSK CYSTEIN RICH DOMAIN IN AUTOIMMUNE MYASTHENIC SYNDROME. 7th International Myology Congress, 2022, Nice, France. ⟨hal-04002800⟩
- Axel You, Odessa-Maud Fayet, Solene Maillard, Laureline Bétemps, Nadine Dragin, et al.. Development of a new experimental Myasthenia Gravis mouse model.. MYOLOGY 2022, 2022, Nice, France. ⟨hal-03861640⟩
- Anne-Charlotte Lefranc, Samy Hamadache, Charles Grosjean, Nadine Dragin. IL-17, SKELETAL MUSCLE AND MYASTHENIA GRAVIS. SFI 2021, Dec 2021, Paris, France. ⟨hal-03844152⟩
- Scott Thomas, Odessa-Maud Fayet, Frédérique Truffault, Elie Fadel, Bastien Provost, et al.. Altered expression of fragile X mental retardation-1 (FMR1) in the thymus in autoimmune myasthenia gravis. Journal of Neuroinflammation, 2021, 18 (1), ⟨10.1186/s12974-021-02311-y⟩. ⟨hal-03441468⟩
- Alexandra Bayer Wildberger, Natalia Pinzon, Axel You, Frédérique Truffault, Aurélien Corneau, et al.. Conditioned Mesenchymal Stromal Cells as tools for immunomodulation in Myasthenia Gravis. 15th Congress of the International Society of NeuroImmunology, Nov 2021, Virtual congress, France. ⟨hal-03440270⟩
- 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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