Experimental paraprotein neuropathy, demyelination by passive transfer of human IgM anti-myelin-associated glycoprotein

Ann Neurol. 1993 May;33(5):502-6. doi: 10.1002/ana.410330514.


Circulating monoclonal IgM antibodies that react with myelin-associated glycoprotein are strongly associated with a specific type of human peripheral nerve demyelination. There has been great interest in this syndrome because, if the paraprotein could be shown to cause the demyelination, then it would be the first proven example of antibody-mediated demyelination in humans. Systemic transfusion of chickens with monoclonal IgM antibody isolated from one of these patients produced peripheral demyelination highly characteristic of the human syndrome. The experimental lesion consists of segmental demyelination and remyelination with minimal inflammation, specific antibody bound to myelin, and widening of the myelin lamellae. In the experimental model, antibody is concentrated in specialized myelin structures, the nodes of Ranvier, and Schmidt-Lanterman incisures, suggesting that myelin-associated glycoprotein may be the antigenic target in vivo. This demonstration that human myelin-associated glycoprotein antibodies cause demyelination in vivo is the final information needed to prove that this type of human demyelination is antibody mediated. This strengthens the proposition that nerve antibodies, present in other human neurological syndromes, may also cause disease.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / analysis
  • Antibodies, Monoclonal / blood*
  • Chickens
  • Demyelinating Diseases / immunology*
  • Demyelinating Diseases / pathology
  • Demyelinating Diseases / physiopathology*
  • Humans
  • Immunization, Passive*
  • Immunoglobulin M / administration & dosage
  • Immunoglobulin M / analysis
  • Immunoglobulin M / blood*
  • Male
  • Microscopy, Electron
  • Myelin Proteins / immunology*
  • Myelin-Associated Glycoprotein
  • Nerve Fibers / ultrastructure
  • Paraproteinemias / immunology*
  • Paraproteinemias / physiopathology*
  • Paraproteinemias / therapy
  • Plasmapheresis
  • Sciatic Nerve / pathology*
  • Sciatic Nerve / ultrastructure


  • Antibodies, Monoclonal
  • Immunoglobulin M
  • Myelin Proteins
  • Myelin-Associated Glycoprotein