The Origin of Anti-GM sub(1) Antibodies in Neuropathies: The "Binding Site Drift" Hypothesis

• Published in: Neurochemical research Vol. 27; no. 7-8; pp. 687 - 695
• Main Authors: Lopez, PHH, Lardone, R D, Irazoqui, F J, Maccioni, M, Nores, G A
• Format: Journal Article
• Language: English
• Published: 01-08-2002
• ISSN: 0364-3190

Elevated titers of serum antibodies against GM sub(1)-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 super(+) B-lymphocytes and that antigen mimicry is involved. Anti-GM sub(1) IgM-antibodies in the normal human immunological repertoire are low affinity antibodies that cross-react with other glycoconjugates carrying Gal beta 1-3GalNAc and probably do not have GM sub(1)-mediated biological activity. Other anti-GM sub(1) 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-GM sub(1) 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".