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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- R. Le Panse, V. Mitev, Louis L. Houdebine, B. Coulomb. Protein kinase C-independent activation of mitogen-activated protein kinase by epidermal growth factor in skin fibroblasts. European Journal of Pharmacology, 1996, 307, pp.339-345. ⟨hal-02688152⟩
- J Vilquin, E Wagner, I Kinoshita, R Roy, J Tremblay. Successful histocompatible myoblast transplantation in dystrophin-deficient mdx mouse despite the production of antibodies against dystrophin.. Journal of Cell Biology, 1995, 131 (4), pp.975-988. ⟨10.1083/jcb.131.4.975⟩. ⟨hal-03824128⟩
- J.T. Vilquin, I. Kinoshita, R. Roy, J.P. Tremblay. Cyclophosphamide immunosuppression does not permit successful myoblast allotransplantation in mouse. Neuromuscular Disorders, 1995, 5 (6), pp.511-517. ⟨10.1016/0960-8966(95)00011-b⟩. ⟨hal-03824453⟩
- Jean-Thomas Vilquin, Benoît Guérette, Ikuo Kinoshita, Brigitte Roy, Marlyne Goulet, et al.. FK506 Immunosuppression to Control the Immune Reactions Triggered by First-Generation Adenovirus-Mediated Gene Transfer. Human Gene Therapy, 1995, 6 (11), pp.1391-1401. ⟨10.1089/hum.1995.6.11-1391⟩. ⟨hal-03824124⟩
- Isabelle Asselin, Martine Tremblay, Jean-Thomas Vilquin, Benoît Guérette, R. Roy, et al.. Quantification of normal dystrophin mRNA following myoblast transplantation in mdx mice. Muscle & Nerve, 1995, 18 (9), pp.980-986. ⟨10.1002/mus.880180909⟩. ⟨hal-03824455⟩
- Ikuo Kinoshita, Jean-Thomas Vilquin, Jacques Tremblay. Pretreatment of myoblast cultures with basic fibroblast growth factor increases the efficacy of their transplantation in mdx mice. Muscle & Nerve, 1995, 18 (8), pp.834-841. ⟨10.1002/mus.880180806⟩. ⟨hal-03824143⟩
- P.F. Kennel, J.T. Vilquin, S. Braun, P. Fonteneau, J.M. Warter, et al.. Myasthenia Gravis: Comparative Autoantibody Assays Using Human Muscle, TE671, and Glucocorticoid-Treated TE671 Cells as Sources of Antigen. Clinical immunology and immunopathology, 1995, 74 (3), pp.293-296. ⟨10.1006/clin.1995.1042⟩. ⟨hal-03824130⟩
- V. Mitev, R. Le Panse, B. Coulomb, L. Miteva, Louis L. Houdebine. Epidermal growth factor stimulates mitogen-activated protein kinase by a PKC-dependent pathway in human keratinocytes. Biochemical and Biophysical Research Communications, 1995, 208 (1), pp.245-252. ⟨hal-02704693⟩
- Isabelle Asselin, Jean Thomas Vilquin, Jacques Tremblay, Benoǐt Guérette, Raynald Roy. Lymphocyte infiltration following allo-and xenomyoblast transplantation in mdx mice. Muscle & Nerve, 1995, 18 (1), pp.39-51. ⟨10.1002/mus.880180107⟩. ⟨hal-03824468⟩
- Ikuo Kinoshita, Jean-Thomas Vilquin, Benoǐt Guérette, Isabelle Asselin, Raynald Roy, et al.. Very efficient myoblast allotransplantation in mice under FK506 immunosuppression. Muscle & Nerve, 1994, 17 (12), pp.1407-1415. ⟨10.1002/mus.880171210⟩. ⟨hal-03824133⟩
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