Seronegative myasthenia gravis: clinical features, response to therapy and synthesis of acetylcholine receptor antibodies in vitro

Abstract

Circulating autoantibodies against the acetylcholine receptor (AChR-Ab) are an important diagnostic tool in myasthenia gravis (MG). Lack of antibodies may cast doubt upon the diagnosis, the immune-mediated mechanism and the nature of the antigen. We examined clinical and laboratory features, response to immunotherapy and production of AChR-Ab in vitro, in 12 seronegative MG patients who were followed up for 2-30 years. It was possible to divide those patients into 2 groups: 7 patients with systemic muscle weakness, with a severe disease and with response to immunosuppressive therapies. The other group of 5 patients was characterized by oculobulbar symptomatology, a relatively benign course and immunotherapy was ineffective in 3 treated patients. Five patients underwent thymectomy and gland histology was normal in all of them. In none of 9 patients examined, were AChR-Ab synthesized in vitro (compared to 65% of seropositive myasthenic patients). Thus seronegative generalized MG is probably an autoimmune disease though the autoantigen is presently unknown and is responsive to immunosuppressive treatment. Seronegative oculobulbar MG might represent a separate disease entity in which immunological mechanisms play no significant role.