Myasthenia gravis induced by monoclonal antibodies to acetylcholine receptors

Vanda A. Lennon, Edward H. Lambert

Research output: Contribution to journalArticlepeer-review

158 Scopus citations


Autoantibodies to nicotinic acetylcholine receptors (AChRs) are demonstrable in sera of approximately 90% of patients with myasthenia gravis (MG), a disease of neuromuscular transmission1. The consistent abnormality in MG is a low amplitude of miniature endplate potentials ( due to decreased sensitivity of the postsynaptic membrane to the neurotransmitter, acetylcholine (ACh). This reflects a decrease in numbers of AChRs in the membrane (for review see ref. 2). The pathogenicity of anti- AChR antibodies has been documented in vivo by passive transfer of MG from human to mouse3 and from rat to rat4 and in vitro on cultured muscle cells5-8. However, titres of anti-AChR antibodies in serum do not correlate closely with severity of muscle weakness in MG patients 1. This lack of correlation very probably reflects the heterogeneity of specificities of anti-AChR antibodies which is known to exist in MG 2. For example, antibodies directed to determinants of AChRs which are inaccessible in vivo may be generated in the course of the disease without being relevant to disease pathogenesis. Identification of antigenic determinants of AChRs which are the primary target(s) of antibody attack in MG is a logical prerequisite to designing antigen-specific immunotherapy for this disease. We report here the production by hybridoma cells of monoclonal rat antibodies reactive with muscle AChR, both adult and fetal, in all of six mammalian species studied. Antibodies produced by two of these hybridoma lines bound to one or more antigenic determinant(s) exposed extracellularly, but remote from the binding site for cholinergic ligands, in the postsynaptic membrane of muscle, and caused a defect of neuromuscular transmission in mice, rats and guinea pigs. These findings establish conclusively that neuromuscular transmission can be impaired by monospecific anti-AChR antibodies which do not inhibit the binding of neurotransmitter to its receptor site.

Original languageEnglish (US)
Pages (from-to)238-240
Number of pages3
Issue number5762
StatePublished - 1980

ASJC Scopus subject areas

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