The origin of anti-GM1 antibodies in neuropathies: The "binding site drift" hypothesis

Pablo Lopez, R. D. Lardone, F. J. Irazoqui, M. Maccioni, G. A. Nores

Research output: Contribution to journalArticle

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".

Original languageEnglish (US)
Pages (from-to)687-695
Number of pages9
JournalNeurochemical Research
Volume27
Issue number7-8
DOIs
StatePublished - Aug 2002
Externally publishedYes

Fingerprint

Anti-Idiotypic Antibodies
Binding Sites
Antibodies
Molecular Mimicry
G(M1) Ganglioside
Genetic Drift
Glycoconjugates
Antibody Affinity
Immunoglobulin M
Autoantibodies
B-Lymphocytes
Lymphocytes
Mutation
Bioactivity
Serum
Antigens
anti-IgM

Keywords

  • Anti-GM antibodies
  • Antigen mimicry
  • Autoimmune neuropathy
  • Binding site drift
  • Binding site expansion
  • Gangliosides

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry

Cite this

The origin of anti-GM1 antibodies in neuropathies : The "binding site drift" hypothesis. / Lopez, Pablo; Lardone, R. D.; Irazoqui, F. J.; Maccioni, M.; Nores, G. A.

In: Neurochemical Research, Vol. 27, No. 7-8, 08.2002, p. 687-695.

Research output: Contribution to journalArticle

Lopez, Pablo ; Lardone, R. D. ; Irazoqui, F. J. ; Maccioni, M. ; Nores, G. A. / The origin of anti-GM1 antibodies in neuropathies : The "binding site drift" hypothesis. In: Neurochemical Research. 2002 ; Vol. 27, No. 7-8. pp. 687-695.
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