Myasthenic antibodies cross-link acetylcholine receptors to accelerate degradation

N Engl J Med. 1978 May 18;298(20):1116-22. doi: 10.1056/NEJM197805182982004.


The decrease of acetylcholine receptors at neuromuscular junctions of myasthenic patients has been attributed to an antibody-mediated autoimmune process that accelerates receptor degradation. We studied the mechanism of this process in skeletal-muscle cultures, using intact antibodies and antibody fragments. Addition of myasthenic IgG or its divalent fragment, F(ab')2, to cultures accelerated the rate of acetylcholine-receptor degradation threefold. By contrast, the monovalent fragment, Fab, from myasthenic serum had no effect on degradation, although it bound to acetylcholine receptors. Addition of a second, "piggyback" antibody to cross-link the Fab:receptor complexes resulted in a threefold increase of the degradation rate. Similarly, when acetylcholine receptors with bound alpha-bungarotoxin were cross-linked by the addition of specific antibody against alpha-bungarotoxin, the degradation rate increased approximately threefold. The effect of myasthenic patients' antibodies in accelerating degradation of acetylcholine receptors is attributed to their ability to cross-link the receptors.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Autoantibodies*
  • Bungarotoxins / immunology
  • Culture Techniques
  • Humans
  • Immunoglobulin Fab Fragments
  • Immunoglobulin G
  • Models, Biological
  • Myasthenia Gravis / immunology*
  • Receptors, Cholinergic / immunology
  • Receptors, Cholinergic / metabolism*


  • Autoantibodies
  • Bungarotoxins
  • Immunoglobulin Fab Fragments
  • Immunoglobulin G
  • Receptors, Cholinergic