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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- Judith Merrheim, José Villegas, Jérôme van Wassenhove, Rémi Khansa, Sonia Berrih-Aknin, et al.. Estrogen, estrogen-like molecules and autoimmune diseases. Autoimmunity Reviews, 2020, 19 (3), pp.102468. ⟨10.1016/j.autrev.2020.102468⟩. ⟨hal-03824055⟩
- Guotian Luo, Joseph Paquet, Julie Boisselier, Adeline Gand, Adrien Moya, et al.. Enzyme-controlled, Nutritive Hydrogel For Mesenchymal Stem Cell Survival And Paracrine Functions. Orthopaedic Research Society, Feb 2020, Phenix, United States. ⟨hal-02365029⟩
- Mélanie A Cron, Emilie Guillochon, Linda Kusner, Rozen Le Panse. Role of miRNAs in Normal and Myasthenia Gravis Thymus. Frontiers in Immunology, 2020, 1, pp.1074. ⟨10.3389/fimmu.2020.01074⟩. ⟨hal-02897998⟩
- Frédérique Truffault, Dani Nazzal, Julien Verdier, Angeline Gradolatto, Elie Fadel, et al.. Comparative Analysis of Thymic and Blood Treg in Myasthenia Gravis: Thymic Epithelial Cells Contribute to Thymic Immunoregulatory Defects. Frontiers in Immunology, 2020, 11, pp.782. ⟨10.3389/fimmu.2020.00782⟩. ⟨hal-02970791⟩
- Mélanie A Cron, Cloé A Payet, Odessa-Maud Fayet, Solène Maillard, Frédérique Truffault, et al.. Decreased expression of miR-29 family associated with autoimmune myasthenia gravis. Journal of Neuroinflammation, 2020, 17 (1), pp.294. ⟨10.1186/s12974-020-01958-3⟩. ⟨hal-02978703⟩
- Alexandra Clarissa Bayer Wildberger, Jean-Thomas Vilquin. Évidence préclinique de l’effet thérapeutique de l’efgartigimod dans un modèle de myasthénie anti-MuSK. Les Cahiers de Myologie, 2020, 21, pp.21 - 22. ⟨10.1051/myolog/202021004⟩. ⟨hal-03082187⟩
- Claire Mj Lefeuvre, Cloé Payet, Odessa-Maud Fayet, Solène Maillard, Frédérique Truffault, et al.. Risk factors associated with myasthenia gravis in thymoma patients: The potential role of thymic germinal centers. Journal of Autoimmunity, 2020, 106, pp.102337. ⟨10.1016/j.jaut.2019.102337⟩. ⟨pasteur-02315094⟩
- Jean-Thomas Vilquin, Serge Braun. Thérapie cellulaire des maladies musculaires Un avenir à l'aune d'une comparaison des progéniteurs. Médecine/Sciences, 2019, Hors-série N°2, 35, pp.7-10. ⟨hal-02356327⟩
- Jose Adolfo Villegas, Jerôme van Wassenhove, Judith Merrheim, Karen Matta, Frédérique Truffault, et al.. Beneficial effects of blocking the IL-23/Th17 pathway in a humanized preclinical MG model. sfi 2019, Nov 2019, Nantes, France. ⟨hal-03843606⟩
- Judith Merrheim, Jérôme van Wassenhove, Bastien Ducreux, Régine Roussin, Sonia Berrih-Aknin, et al.. Effect of AhR ligands on thymic epithelial cell differentiation and function. SFI 2019, Nov 2019, Nantes, France. ⟨hal-03843650⟩
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