Résumé :
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Communication n° 448 Myasthenia Gravis (MG) is an autoimmune disease mediated by antibodies directed against the acetylcholine receptor (AChR), which are found in about 85% of patients. Autoimmune experimental MG (EAMG) can be induced in rats by immunization with Torpedo AChR. In MG and EAMG, anti-AChR antibodies bind to AChR and induce its internalization and degradation, which results in AChR decreased expression and impaired neuromuscular transmission leading to myasthenic symptoms. However the molecular mechanisms associated with AChR loss are not known. We used the transcriptomic approach to analyze (by Agilent cDNA chips) the expression of muscle genes in biopsies from MG patients that have anti-AChR antibodies as compared to controls. In parallel, we performed a similar analysis (by Affymetrix chips) in myasthenic rats and then compared the lists of dysregulated genes in MG and EAMG. Statistical analyses revealed two major groups of dysregulated genes common to both MG and EAMG: 1) Genes linked to muscle biology (p values 0.0 and p<0.0003 for human and rat, respectively) including muscle proteins regulating contraction such as myosin polypeptides and myosin binding proteins; 2) Genes belonging to the chaperone protein category including several heat shock proteins (p values < 0.0004 and p<0.0003 for human and rat, respectively). Besides these major categories, in human MG patients there was also evidence for dysregulation of genes involved in transcription and translation, while in EAMG rats, genes involved in metabolism and cell death were overrepresented. Finally, in both MG and EAMG there were no inflammation-associated dysregulated genes. In conclusion, these results show that the pathological mechanisms taking place in the muscle of MG patients and EAMG rats are essentially similar. Since muscle genes are clearly dysregulated as a result of the autoimmune attack, modulating these genes could represent a new therapeutical approach for myasthenia.
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