title: The origin of anti-GM1 antibodies in neuropathies: the "binding site drift" hypothesis.
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-GM, IgM-antibodies in the normal human immunological repertoire are low affinity antibodies that cross-react with other glycoconjugates carrying Gal beta1-3GalNAc 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".
authors.affiliation: CIQUIBIC-CONICET and Departamento de Química Biológica Dr. Ranwel Caputto, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina.
authors.forename: Pablo H H
authors.initials: PH
authors.lastname: Lopez
authors.forename: Ricardo D
authors.initials: RD
authors.lastname: Lardone
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Irazoqui
authors.forename: Mariana
authors.initials: M
authors.lastname: Maccioni
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Nores
mesh_terms: D001323:Autoantibodies / Q000276:immunology*; D001666:Binding Sites, Antibody; D005677:G(M1) Ganglioside / Q000276:immunology*; D006801:Humans
chemical_list: D001323:Autoantibodies; D005677:G(M1) Ganglioside