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 |
|---|
- Mridul Johari, Daphne Wijnbergen, Alaa Khan, Pedro Machado, Henry Houlden, et al.. Elucidating the molecular biology of Inclusion body Myositis through multi-omics analysis. Solve-RD, Solving the unsolved Rare Diseases, Final Meeting 2023, Apr 2023, Prague, Czech Republic. ⟨hal-04086230⟩
- Tanya Stojkovic, Marion Masingue, Helène Turmel, Marianne Hezode-Arzel, Anthony Béhin, et al.. Diagnostic yield of a practical electrodiagnostic protocol discriminating between different congenital myasthenic syndromes. Neuromuscular Disorders, 2022, 32 (11-12), pp.870-878. ⟨10.1016/j.nmd.2022.10.001⟩. ⟨hal-03993811⟩
- Olivier Benveniste. Refractory myositides.. XVIth UCLouvain Review Course on Systemic Rheumatic Diseases, Nov 2022, Bruxelles, Belgium. ⟨hal-03864159⟩
- Olivier Benveniste. Les myopathies inflammatoires en 2022 : de la physiopathologie aux traitements ciblés. 17ème Journées Scientifiques de la Société Tunisienne d’Immunologie, Nov 2022, Hammamet, Tunisie. ⟨hal-03864162⟩
- Océane Landon-Cardinal, Perrine Guillaume-Jugnot, Ségolène Toquet, Nabiha Sbeih, Aude Rigolet, et al.. JAK inhibitors for the treatment of adult dermatomyositis: A pilot study. Journal of The American Academy of Dermatology, 2022, ⟨10.1016/j.jaad.2022.10.055⟩. ⟨hal-03996988⟩
- Alexandrine Mahoudeau, Céline Anquetil, Nozomu Tawara, Hossein Khademian, Damien Amelin, et al.. Myostatin in idiopathic inflammatory myopathies: Serum assessment and disease activity. Neuropathology and Applied Neurobiology, 2022, ⟨10.1111/nan.12849⟩. ⟨hal-03830849⟩
- Yves Allenbach. 256th ENMC International Workshop: Myositis specific autoantibodies (MSAab). 13ième Journée Interdisciplinaire du Muscle Inflammatoire, Sep 2022, Paris, France. ⟨hal-03835350⟩
- Yves Allenbach. Quoi de neuf dans la prise en charge des dermatomyosites à anti-MDA5 sévères ?. 13ième Journée du Muscle Inflammatoire, Sep 2022, Paris, France. ⟨hal-03835354⟩
- Debora Pehl, Corinna Preuße, Yves Allenbach, Olivier Benveniste, Philipp Dittert, et al.. Eosinophilic fasciitis (Shulman syndrome)—recognition of the histological spectrum allows for new insights into possible pathomechanisms. Rheumatology, 2022, ⟨10.1093/rheumatology/keac526⟩. ⟨hal-03830836⟩
- Olivier Benveniste. Inflammatory Myopathies and Innovative Therapies. TMA’s Annual Patient Conference, Sep 2022, Orlando, United States. ⟨hal-03864169⟩
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