Résumé :
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Communication n° 512 The Aquired Autoimmune Myasthenia Gravis (MG) is characterized by 3 immunological entities : seropositive MG (SPMG), seronegative MG (SNMG) and MuSK+. Despite the different immunological profile, all MG patients present the major symptoms of the disease: pathological muscle weakness and fatigue. This raises the question: Are the pathogenic mechanisms at the neuromuscular junction identical? Objective: to compare the expression of the molecules at the postsynaptic membrane of the neuromuscular junction (NMJ). Total RNA was extracted from muscular biopsies obtained after thymectomy of 31 MG patients. Controls biopsies were taken during cardiac surgery. Messenger RNA expression of proteins involved in the neuro-muscular transmission and the stability of the post synaptic structures of the NMJ was checked by real time quantitative RT-PCR. Using microarray technique we compared SPMG, SNMG to a reference normal muscle in attempt to discover new possible targets of the autoimmune attack. We found that AChR alpha, MuSK, ErbB3, ErbB4 and Rapsyn were overexpressed in more severe disease and the serology had no influence on their expression. Not surprisingly, all the genes studied were globally overexpressed in MG patients in comparison with controls. The transcriptome analysis showed that in both SPMG and SNMG, the subcategories of upregulated genes were essentially involved in muscle development and in chaperone activity, while that of down regulated genes was extracellular matrix category. Our results show correlation between the disease severity and the overexpression of the genes tested, regardless the immunological findings. Altogether these data suggest the existence of a compensatory mechanism regulating the expression of several genes involved in the neuromuscular junction. Most dysregulated genes are common between SNMG and SNPG patients, suggesting common mechanisms of autoimmune attack in these groups of patients.
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