Résumé :
|
Communication n° 480 Introduction : MuSK positive (MuSK+) myasthenia gravis (MG), representing approximately 40% of the patients with seronegative MG (SNMG) is more severe disease, affecting predominantly the neck, bulbar and respiratory muscles, and causing frequent respiratory crises. Clinical and EMG signs of muscle atrophy are found in some patients. Objective : To explore the pathogenic effect of sera from MuSK+ MG patients. Methods : MuSK+ MG sera or anti-MuSK polyclonal antibodies were added to TE 671 cells and their effect on the cell morphology, proliferation and differentiation was compared to that of sera from healthy controls, SNMG or patients with anti-AChR antibodies (SPMG). 3H-Thymidine and CFSE incorporation were used in the cell proliferation experiments. Messenger RNA expression of the markers of muscle cell differentiation and atrophy was measured by real-time RT-PCR. Results : Approximately 50% of the MuSK+ MG sera changed TE 671 cell morphology towards elongated, multinucleated myotube-like cells. These changes were accompanied by time- and dose dependent perturbation of cell proliferation, overexpression of the muscle differentiation (myogenin and troponin) and atrophy (atrogin and MuRF1) markers and were muscle cell specific. The effects of the polyclonal anti-MuSK AB were similar to that caused by the patients' sera. None of the control, SPMG, SNMG had any effect on the TE 671 morphology and growth. Conclusions : Some MuSK+ MG sera convert TE 671 from proliferation toward cell differentiation. As the polyclonal anti-MuSK AB had similar effect, we could conclude that the latter is the primary cause of this phenomenon. The overexpression of the muscle atrophy markers could account for the clinical findings in some patients with MuSK+ MG.
|