Functional activities of autoantibodies to acetylcholine receptors and the clinical severity of myasthenia gravis

N Engl J Med. 1982 Sep 23;307(13):769-75. doi: 10.1056/NEJM198209233071301.


The pathogenesis of myasthenia gravis involves a humorally mediated autoimmune attack directed against acetylcholine receptors of skeletal muscles. Antibodies against acetylcholine receptors are detected in the serum of more than 80 per cent of patients, but the antibody titers correspond poorly with the severity of disease. To distinguish between antibody titers and antibody activity, we measured the ability of serum immunoglobulin from 49 patients to induce accelerated degradation or blockade of the binding sites of acetylcholine receptors, using a mammalian skeletal-muscle tissue-culture system. Immunoglobulin from 41 of 45 patients tested (91 per cent) increased the rate of degradation of acetylcholine receptors, and the relative increase in the degradation rate corresponded closely (P less than 0.001) with clinical status. Immunoglobulin from 42 of 48 patients tested (88 per cent) produced blockade of receptors, and the extent of the blockade also corresponded with clinical status (P less than 0.001). An index of the combined activities of the immunoglobulin in accelerating degradation and producing blockade of acetylcholine receptors was elevated in 43 of 44 patients (98 per cent) whose immunoglobulins were tested for both activities; this index predicted the patients' clinical status significantly better (P less than 0.001) than either measure alone. This finding suggests that the functional ability of antibodies to decrease the number of available acetylcholine receptors by these two mechanisms is clinically relevant in the pathogenesis of myasthenia gravis.

Publication types

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

MeSH terms

  • Autoantibodies / immunology*
  • Binding Sites
  • Culture Techniques
  • Female
  • Humans
  • Immunoglobulins / immunology
  • Male
  • Muscles / immunology
  • Myasthenia Gravis / classification
  • Myasthenia Gravis / diagnosis
  • Myasthenia Gravis / immunology*
  • Receptors, Cholinergic / immunology*
  • Receptors, Cholinergic / metabolism


  • Autoantibodies
  • Immunoglobulins
  • Receptors, Cholinergic