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 |
|---|
- 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. Etiological and Pathophysiological Mechanisms in Myasthenia Gravis. 15th International Congress of Neuroimmunology (ISNI), 2021, Nice (Virtual), France. ⟨hal-03861666⟩
- Claire Lefeuvre, Cloé Payet, Odessa-Maud Fayet, Solène Maillard, Frédérique Truffault, et al.. Risk factors associated with myasthenia gravis in thymoma patients: a link with ectopic germinal centers. 12th International Congress on Autoimmunity, 2021, Athènes (Virtual), Greece. ⟨hal-03861873⟩
- Jean-Thomas Vilquin, Alexandra Bayer, Rozen Le Panse, Sonia Berrih-Aknin. The muscle is not a passive target in Myasthenia Gravis. Frontiers in Neurology, 2020, 10, pp.1343. ⟨hal-02396099⟩
- Inès Barthélémy, Jean-Laurent Thibaud, Pauline de Fornel, Marco Cassano, Isabel Punzon, et al.. In vivo stem cell tracking using scintigraphy in a canine model of DMD. Scientific Reports, 2020, 10 (1), ⟨10.1038/s41598-020-66388-w⟩. ⟨hal-02888783⟩
- Jessy Etienne, Pierre Joanne, Cyril Catelain, Stéphanie Riveron, Alexandra Clarissa Bayer, et al.. Targeting aldehyde dehydrogenase to mitigate the physiopathology of Duchenne muscular dystrophy. 3rd Victorian Muscle Network Symposium 2020, Oct 2020, Virtual Congress, Australia. ⟨hal-03440309⟩
- Jessy Etienne, Pierre Joanne, Cyril Catelain, Stéphanie Riveron, Alexandra Bayer Wildberger, et al.. The authors reply: Comment on: “Aldehyde dehydrogenases contribute to skeletal muscle homeostasis in healthy, aging, and Duchenne muscular dystrophy patients” by Etienne et al.. Journal of Cachexia, Sarcopenia and Muscle, 2020, ⟨10.1002/jcsm.12629⟩. ⟨hal-03038617⟩
- Anna Rostedt Punga, Linda Kusner, Sonia Berrih-Aknin, Rozen Le Panse. Editorial: Advances in Autoimmune Myasthenia Gravis. Frontiers in Immunology, 2020, ⟨10.3389/fimmu.2020.01688⟩. ⟨hal-03052107⟩
- Jessy Etienne, Pierre Joanne, Cyril Catelain, Stéphanie Riveron, Alexandra Clarissa Bayer, et al.. Aldehyde dehydrogenases contribute to skeletal muscle homeostasis in healthy, aging, and Duchenne muscular dystrophy patients. Journal of Cachexia, Sarcopenia and Muscle, 2020, 11 (4), pp.1047-1069. ⟨10.1002/jcsm.12557⟩. ⟨hal-03082621⟩
- Isabel Punzón, David Mauduit, Bryan Holvoet, Jean-Laurent Thibaud, Pauline de Fornel, et al.. In Vivo Myoblasts Tracking Using the Sodium Iodide Symporter Gene Expression in Dogs. Molecular Therapy - Methods and Clinical Development, 2020, 17, pp.317-327. ⟨10.1016/j.omtm.2019.12.011⟩. ⟨hal-03082528⟩
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