Myasthenia Gravis — Study of Humoral Immune Mechanisms by Passive Transfer to Mice

Abstract

To study the role of humoral factors in the pathogenesis of myasthenia gravis, we employed passive transfer of human serum fractions to mice. Immunoglobulins from 16 patients with myasthenia gravis were injected into mice daily for one to 14 days. Typical myasthenic features of reduction in amplitude of miniature end-plate potentials (mean change more than 50 per cent, P<0.005) or reduction in acetylcholine receptors at neuromuscular junctions (mean change more than 50 per cent, P<0.005) (or both) were produced by immunoglobulin from 15 of the 16 patients. Some mice showed weakness or decremental responses to repetitive nerve stimulation as well. The active fraction was identified as IgG by three different purification methods. Its effect was enhanced by the third component (C3) of the complement system, but the fifth component (C5) had no effect. These data suggest that the pathogenesis of myasthenia gravis often involves an antibody-mediated autoimmune attack on the acetylcholine receptors of the neuromuscular junction. (N Engl J Med 296:125–131, 1977)