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 |
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- Alexandra Bayer Wildberger, Judith Lorant, Jean-Thomas Vilquin. Les exosomes, des messagers intercellulaires naturels aux mécanismes polyvalents pour le traitement des myopathies?. Les Cahiers de Myologie, 2021, 37 (1), pp.44-45. ⟨hal-03440216⟩
- Lucie Isoline Pisella, Sara Fernandes, Guilhem Sole, Tanya Stojkovic, Celine Tard, et al.. A multicenter cross-sectional French study of the impact of COVID-19 on neuromuscular diseases. Orphanet Journal of Rare Diseases, 2021, 16 (1), pp.450. ⟨10.1186/s13023-021-02090-y⟩. ⟨hal-03470914⟩
- Cloé Payet. Study of Interferon type I in Myasthenia Gravis. Human health and pathology. Sorbonne Université, 2021. English. ⟨NNT : 2021SORUS517⟩. ⟨tel-03783511⟩
- S Birnbaum, R Porcher, P Portero, B Clair, S Demeret, et al.. Home-based exercise in autoimmune myasthenia gravis: A randomized controlled trial. Neuromuscular Disorders, 2021, 31 (8), pp.726-735. ⟨10.1016/j.nmd.2021.05.002⟩. ⟨hal-03442076⟩
- Sonia Berrih-Aknin, Kristl G Claeys, Nancy Law, Renato Mantegazza, Hiroyuki Murai, et al.. Patient-reportedimpact of myasthenia gravis in the real world: protocol for a digital observational study (MyRealWorld MG). BMJ Open, 2021, 11 (7), pp.e048198. ⟨10.1136/bmjopen-2020-048198⟩. ⟨hal-03296042⟩
- Judith Merrheim, Sonia Berrih-Aknin, Rozen Le Panse, Nadine Dragin. AhR ligands effects on thymic epithelial cell differentiation and function. 12th international congress on autoimmunity, May 2021, virtual, France. ⟨hal-03844091⟩
- Alexandra Bayer Wildberger, José Villegas, Julien Verdier, Mariette Giannini, Solène Maillard, et al.. Will Mesenchymal Stromal Cells become tools for immunomodulation in Myasthenia Gravis ?. 12th International Congress on Autoimmunity, May 2021, Virtual Congress, Greece. ⟨hal-03440251⟩
- Jose Adolfo Villegas, Sonia Berrih-Aknin, Rozen Le Panse, Nadine Dragin. Blocking the IL-23/Th17 pathway ameliorates myasthenia gravis symptoms in autoimmune myasthenia gravis mouse model. 12th international congress on autoimmunity, May 2021, virtual, France. ⟨hal-03844107⟩
- Cloé Payet. Study of interferon type I signature in autoimmune Myasthenia Gravis. 12th International Congress on Autoimmunity, 2021, Athènes (Virtual), Greece. ⟨hal-03861863⟩
- Rozen Le Panse. Early onset and Juvenile Myasthenia Gravis. 16th International Congress on Neuromuscular Diseases (ICNMD 2021), 2021, Valencia (Virtual), Spain. ⟨hal-03861656⟩
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