Myasthenia gravis: übertragbarer "myasthenogener" Faktor im Serum von Patienten - Elektrophysiologische und radiochemische Untersuchungen

Recent evidence indicates that patients with myasthenia gravis (MG) have a reduced number of acetylcholine receptors (Ach-R) at the neuromuscular junction. It has been shown that this abnormality by itself, when produced experimentally, may induce all electrophysiological signs of MG. Furthermore, autoantibodies against human Ach-R have been detected in the serum of patients with MG. It has been proposed that serum autoantibodies may produce the symptomatology of the disease. The purpose of this study was to evaluate whether prolonged exposure to a MG serum fraction in vivo might serve to bring about the myasthenic disorder. A 33% ammonium sulfate precipitated fraction of serum from 9 patients with MG was injected daily into BDF₁ mice for up to 14 days. The amount of IgG in this fraction equaled 10-15 mg per single injection. The mice showed reduced amplitudes of the miniature endplate potentials in the diaphragm (mean reduction by 65%), and a reduced number of Ach-R available for ¹²⁵I-α-bungarotoxin binding (mean reduction by 38% in the extensor digitorum m. and 54% in the soleus m.). In some of the mice a decremental response on repetitive nerve stimulation and clinical signs of muscle weakness could also be demonstrated. None of the animals injected with the immunoglobulin fraction from control sera developed these abnormalities. The results indicate that the immunoglobulin fraction of MG serum contains a transferable "myasthenogenic" factor, presumably an antibody, which is able to bring about many of the characteristic features of MG. These findings provide support for the concept of MG as an autoimmune disease.