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 language | English (US) |
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Pages (from-to) | 687-695 |
Number of pages | 9 |
Journal | Neurochemical Research |
Volume | 27 |
Issue number | 7-8 |
DOIs | |
State | Published - Aug 1 2002 |
Externally published | Yes |
Keywords
- Anti-GM antibodies
- Antigen mimicry
- Autoimmune neuropathy
- Binding site drift
- Binding site expansion
- Gangliosides
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience