The membrane attack pathway of complement drives pathology in passively induced experimental autoimmune myasthenia gravis in mice

Clin Exp Immunol. 2006 Nov;146(2):294-302. doi: 10.1111/j.1365-2249.2006.03205.x.


The human neuromuscular disease myasthenia gravis (MG) is characterized by the generation of autoantibodies reactive with nicotinic acetylcholine receptors (AChR) that cause loss of AChR from the neuromuscular end-plate with resultant failure of neuromuscular transmission. A role for complement (C) in AChR loss has been suggested based upon morphological identification of C at the end-plate in MG and from the effects of C inhibition in murine models. Here we provide further evidence implicating C, and specifically the membrane attack complex (MAC), in a mouse model of MG. Mice deficient in the C regulators Daf1 and/or Cd59a were tested in the model. Wild-type mice were resistant to disease while mice deficient in Daf1 had mild disease symptoms with evidence of C activation and AChR loss at end-plates. Cd59a-deficient mice had very mild disease with some muscle inflammation and essentially undamaged end-plates. In contrast, mice deficient in both C regulators developed a severe paralytic disease with marked muscle inflammation and loss of end-plates. Inhibition of MAC assembly abrogated clinical disease in these double-deficient mice, demonstrating conclusively that MAC formation was driving pathology in the model. These findings provoke us to suggest that current anti-C therapeutics targeting MAC assembly will be beneficial in MG patients resistant to conventional therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • CD55 Antigens / immunology
  • CD59 Antigens / immunology
  • Complement Activation / immunology
  • Complement C3 / metabolism
  • Complement Membrane Attack Complex / immunology*
  • Disease Susceptibility
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Endplate / immunology
  • Myasthenia Gravis, Autoimmune, Experimental / immunology*
  • Myasthenia Gravis, Autoimmune, Experimental / pathology
  • Receptors, Cholinergic / deficiency
  • Receptors, Cholinergic / immunology


  • Antibodies, Monoclonal
  • CD55 Antigens
  • CD59 Antigens
  • Complement C3
  • Complement Membrane Attack Complex
  • Receptors, Cholinergic