Serological diagnostics in myasthenia gravis based on novel assays and recently identified antigens.

Abstract: Myasthenia gravis (MG) is the most common immune-mediated disorder of the neuromuscular junction with a prevalence of 200–300/million population and its study has established paradigms for exploring other antibody-mediated diseases. Most MG patients (~85%) have autoantibodies against the muscle acetylcholine receptor (AChR-MG), whereas about 6% of MG patients have autoantibodies against the muscle specific kinase (MuSK-MG). Until recently no autoantibodies could be detected in the remaining patients (seronegative MG). Probably, the most sensitive assays for the detection of the autoantibodies in MG sera have been the radioimmunoprecipitation assays (RIPA) for both types of MG. However, with recent novel methods, not yet used routinely, it has been shown that the “seronegative” MG group includes patients with low levels of autoantibodies or of low affinity, against the known autoantigens, or even with antibodies to recently identified autoantigens. Since MG is heterogeneous in terms of pathophysiology, depending on the autoantigen targeted and on other factors (e.g. presence of thymoma), the serological tests are crucial in verifying the initial clinical diagnosis, whereas frequent measurement of autoantibody levels is important in monitoring the course of the disease and the efficacy of treatment. In addition, in AChR-MG, autoantibodies against the muscle proteins titin and ryanodin receptor have been identified; these antibodies are useful for the classification of MG, indicating the concomitant presence of thymoma, and as prognostic markers. [Copyright &y& Elsevier]