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Neurochemical Research

, Volume 27, Issue 7–8, pp 687–695 | Cite as

The Origin of Anti-GM1 Antibodies in Neuropathies: The “Binding Site Drift” Hypothesis

  • Pablo H. H. Lopez
  • Ricardo D. Lardone
  • Fernando J. Irazoqui
  • Mariana Maccioni
  • Gustavo A. Nores
Article

Abstract

Elevated titers of serum antibodies against GM1-ganglioside are associated with a variety of autoimmune neuropathies. The origin of these autoantibodies is still unknown, although there is evidence that they are produced by CD5+ B-lymphocytes and that antigen mimicry is involved. Anti-GM1 IgM-antibodies in the normal human immunological repertoire are low affinity antibodies that cross-react with other glycoconjugates carrying Galβ1-3GalNAc and probably do not have GM1-mediated biological activity. Other anti-GM1 IgM-antibodies with higher affinity and/or different fine specificity are present in patients with motor syndromes. Based on our studies of structural requirement for binding, we hypothesize that disease-associated anti-GM1 antibodies originate at random by mutations affecting the binding site of naturally-occurring ones. The hypothesis is conceptually similar to the established phenomenon of “genetic drift” in species evolutionary biology and is therefore termed “binding site drift”.

Gangliosides anti-GM1 antibodies antigen mimicry binding site expansion binding site drift autoimmune neuropathy 

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Copyright information

© Plenum Publishing Corporation 2002

Authors and Affiliations

  • Pablo H. H. Lopez
    • 1
  • Ricardo D. Lardone
    • 1
  • Fernando J. Irazoqui
    • 1
  • Mariana Maccioni
    • 2
  • Gustavo A. Nores
    • 1
  1. 1.CIQUIBIC-CONICET and Departamento de Química Biológica “Dr. Ranwel Caputto,” Facultad de Ciencias QuímicasUniversidad Nacional de CórdobaCórdobaArgentina
  2. 2.Departamento de Bioquímica Clínica, Facultad de Ciencias QuímicasUniversidad Nacional de CórdobaCórdobaArgentina

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