Résumé :
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Anti-acetylcholine receptor (AChR) autoantibodies target the muscle in human spontaneous MG and its induced model experimental autoimmune MG (EAMG). The aim of the study was to identify the common and specific molecular signatures of the muscle pathology in these two diseases. A transcriptomic analysis was performed on muscle tissue from MG patients and their matched healthy controls and from EAMG rats and their CFA-immunized control rats. Most deregulated gene categories were common in MG patients and EAMG rats: the more significant deregulation was associated with muscle development. In addition, deregulation of genes associated with the IL-6 pathway was observed in both MG and EAMG muscles. The expression of IL-6 and its receptor were altered in muscles of EAMG compared to control rats. Most MG sera and some monoclonal anti-AChR antibodies induced a significant increase in IL-6 production by human muscle cells. This antibody-mediated regulation was not due to altered cell proliferation but rather, appears to depend on a transcriptional mechanism. These results show for the first time very marked changes in muscle gene expression in the muscles of MG patients and EAMG rats emphasizing similar pathological mechanisms. Thus, the events occurring in human MG muscle are likely a consequence of the autoimmune attack. Selective anti-AChR antibodies alter IL-6 production, suggesting a putative novel functional mechanism of action of anti-AChR antibodies.
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