Myasthenia gravis (MG) is a chronic neuromuscular disease leading to varying degrees of skeletal muscle weakness. Some of the symptoms of the disorder include weakness of the eye muscles, difficulty in swallowing and slurred speech. It is caused by the failure of neuromuscular transmission mediated by autoantibodies. About 80 to 85% of patients with MG have autoantibodies against acetylcholine receptors (AChR). A subset of patients with MG does not have antibodies to the acetylcholine receptor that can be detected with routine diagnostic testing (seronegative MG, SNMG). MuSK antibodies are only present in some of these patients, and the number varies worldwide. Patients who have seronegative MG and who have antibodies against MuSK can be referred to as having MuSK-MG to distinguish them from patients who have anti-AChR antibodies (AChR-MG). MuSK-MG can be associated with severe bulbar and facial weakness and tongue atrophy. In this paper, Dr. Maria Leite and colleagues explored the possibility that studying antibody binding to tightly clustered AChRs might demonstrate antibody binding to AChRs for patients who were antibody negative by the traditional assay. Their previous research indicated that some SNMG plasmas contain factors that inhibit AChR function. The effect was acute and reversible with washing. This led them to hypothesize that there might be antibodies that did not bind tightly to the AChR and thus were not able to bind to single AChRs floating in solution. These weakly binding antibodies might be able to bind to AChR that are closely packed, as has been demonstrated on the endplate membrane. In this study, they expressed rapsyn along with AChRs in cultured cells. Rapsyn cross-links AChRs producing clusters of closely packed AChRs. They found that more than 50% of the sera from SNMG patients bound to AChR clusters. Therefore about half of the patients who have SNMG when tested with traditional assay techniques may have anti-AChR antibodies that bind weakly to AChRs. The data from this study have important clinical and technical implications for providing the basis of a new assay to detect AChR and other antibodies in myasthenia gravis.


Références : Brain. 2008 Jul;131(Pt 7):1940-52.