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.

Equipe Le Panse au complet
Rozen Le Panse

Contacts :

Rozen Le Panse


Our main publications

  1. Thomas, S, Fayet, OM, Truffault, F, Fadel, E, Provost, B, Hamza, A et al.. Altered expression of fragile X mental retardation-1 (FMR1) in the thymus in autoimmune myasthenia gravis. J Neuroinflammation. 2021;18 (1):270. doi: 10.1186/s12974-021-02311-y. PubMed PMID:34789272 PubMed Central PMC8597299.
  2. Birnbaum, S, Porcher, R, Portero, P, Clair, B, Demeret, S, Eymard, B et al.. Home-based exercise in autoimmune myasthenia gravis: A randomized controlled trial. Neuromuscul Disord. 2021;31 (8):726-735. doi: 10.1016/j.nmd.2021.05.002. PubMed PMID:34304969 .
  3. Cron, MA, Payet, CA, Fayet, OM, Maillard, S, Truffault, F, Fadel, E et al.. Decreased expression of miR-29 family associated with autoimmune myasthenia gravis. J Neuroinflammation. 2020;17 (1):294. doi: 10.1186/s12974-020-01958-3. PubMed PMID:33032631 PubMed Central PMC7545844.
  4. Barthélémy, I, Thibaud, JL, de Fornel, P, Cassano, M, Punzón, I, Mauduit, D et al.. In vivo stem cell tracking using scintigraphy in a canine model of DMD. Sci Rep. 2020;10 (1):10681. doi: 10.1038/s41598-020-66388-w. PubMed PMID:32606364 PubMed Central PMC7327062.
  5. Cron, MA, Guillochon, É, Kusner, L, Le Panse, R. Role of miRNAs in Normal and Myasthenia Gravis Thymus. Front Immunol. 2020;11 :1074. doi: 10.3389/fimmu.2020.01074. PubMed PMID:32587589 PubMed Central PMC7297979.
  6. Punzón, I, Mauduit, D, Holvoet, B, Thibaud, JL, de Fornel, P, Deroose, CM et al.. In Vivo Myoblasts Tracking Using the Sodium Iodide Symporter Gene Expression in Dogs. Mol Ther Methods Clin Dev. 2020;17 :317-327. doi: 10.1016/j.omtm.2019.12.011. PubMed PMID:32577429 PubMed Central PMC7293195.
  7. Truffault, F, Nazzal, D, Verdier, J, Gradolatto, A, Fadel, E, Roussin, R et al.. Comparative Analysis of Thymic and Blood Treg in Myasthenia Gravis: Thymic Epithelial Cells Contribute to Thymic Immunoregulatory Defects. Front Immunol. 2020;11 :782. doi: 10.3389/fimmu.2020.00782. PubMed PMID:32435245 PubMed Central PMC7218102.
  8. Lefeuvre, CM, Payet, CA, Fayet, OM, Maillard, S, Truffault, F, Bondet, V et al.. Risk factors associated with myasthenia gravis in thymoma patients: The potential role of thymic germinal centers. J Autoimmun. 2020;106 :102337. doi: 10.1016/j.jaut.2019.102337. PubMed PMID:31594658 .
  9. Cron, MA, Maillard, S, Truffault, F, Gualeni, AV, Gloghini, A, Fadel, E et al.. Causes and Consequences of miR-150-5p Dysregulation in Myasthenia Gravis. Front Immunol. 2019;10 :539. doi: 10.3389/fimmu.2019.00539. PubMed PMID:30984166 PubMed Central PMC6450174.
  10. Villegas, JA, Bayer, AC, Ider, K, Bismuth, J, Truffault, F, Roussin, R et al.. Il-23/Th17 cell pathway: A promising target to alleviate thymic inflammation maintenance in myasthenia gravis. J Autoimmun. 2019;98 :59-73. doi: 10.1016/j.jaut.2018.11.005. PubMed PMID:30578016 .
  11. Yilmaz, V, Maillard, S, Truffault, F, Bolgert, F, Behin, A, Regnard, JF et al.. Regulatory B cells in myasthenia gravis are differentially affected by therapies. Ann Clin Transl Neurol. 2018;5 (11):1408-1414. doi: 10.1002/acn3.645. PubMed PMID:30480034 PubMed Central PMC6243377.
  12. Villegas, JA, Gradolatto, A, Truffault, F, Roussin, R, Berrih-Aknin, S, Le Panse, R et al.. Cultured Human Thymic-Derived Cells Display Medullary Thymic Epithelial Cell Phenotype and Functionality. Front Immunol. 2018;9 :1663. doi: 10.3389/fimmu.2018.01663. PubMed PMID:30083154 PubMed Central PMC6064927.
  13. Cron, MA, Maillard, S, Delisle, F, Samson, N, Truffault, F, Foti, M et al.. Analysis of microRNA expression in the thymus of Myasthenia Gravis patients opens new research avenues. Autoimmun Rev. 2018;17 (6):588-600. doi: 10.1016/j.autrev.2018.01.008. PubMed PMID:29655674 .
  14. Mariot, V, Joubert, R, Hourdé, C, Féasson, L, Hanna, M, Muntoni, F et al.. Downregulation of myostatin pathway in neuromuscular diseases may explain challenges of anti-myostatin therapeutic approaches. Nat Commun. 2017;8 (1):1859. doi: 10.1038/s41467-017-01486-4. PubMed PMID:29192144 PubMed Central PMC5709430.
  15. Robinet, M, Villeret, B, Maillard, S, Cron, MA, Berrih-Aknin, S, Le Panse, R et al.. Use of Toll-Like Receptor Agonists to Induce Ectopic Lymphoid Structures in Myasthenia Gravis Mouse Models. Front Immunol. 2017;8 :1029. doi: 10.3389/fimmu.2017.01029. PubMed PMID:28970832 PubMed Central PMC5609563.
  16. Dragin, N, Nancy, P, Villegas, J, Roussin, R, Le Panse, R, Berrih-Aknin, S et al.. Balance between Estrogens and Proinflammatory Cytokines Regulates Chemokine Production Involved in Thymic Germinal Center Formation. Sci Rep. 2017;7 (1):7970. doi: 10.1038/s41598-017-08631-5. PubMed PMID:28801669 PubMed Central PMC5554297.
  17. Attia, M, Maurer, M, Robinet, M, Le Grand, F, Fadel, E, Le Panse, R et al.. Muscle satellite cells are functionally impaired in myasthenia gravis: consequences on muscle regeneration. Acta Neuropathol. 2017;134 (6):869-888. doi: 10.1007/s00401-017-1754-2. PubMed PMID:28756524 .
  18. Mamrut, S, Avidan, N, Truffault, F, Staun-Ram, E, Sharshar, T, Eymard, B et al.. Methylome and transcriptome profiling in Myasthenia Gravis monozygotic twins. J Autoimmun. 2017;82 :62-73. doi: 10.1016/j.jaut.2017.05.005. PubMed PMID:28549776 .
  19. Sudres, M, Maurer, M, Robinet, M, Bismuth, J, Truffault, F, Girard, D et al.. Preconditioned mesenchymal stem cells treat myasthenia gravis in a humanized preclinical model. JCI Insight. 2017;2 (7):e89665. doi: 10.1172/jci.insight.89665. PubMed PMID:28405609 PubMed Central PMC5374074.
  20. Dragin, N, Bismuth, J, Cizeron-Clairac, G, Biferi, MG, Berthault, C, Serraf, A et al.. Estrogen-mediated downregulation of AIRE influences sexual dimorphism in autoimmune diseases. J Clin Invest. 2016;126 (4):1525-37. doi: 10.1172/JCI81894. PubMed PMID:26999605 PubMed Central PMC4811157.

AFM Telethon : innover pour guérir
Assistance Publique Hôpitaux de Paris
Agence nationale de la recherche
Région Ile-de-France
SU Emergence
Agence de la Biomédecine
Ahead Therapeutics

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