title: STD-NMR used to elucidate the fine binding specificity of pathogenic anti-ganglioside antibodies directly in patient serum.
abstract: High-resolution binding profiles were elucidated for anti-GM1 IgM autoantibodies from two patients with a progressive form of paraproteinemic polyneuropathy. Antibody-ligand interaction was characterized by generating STD-NMR signals in target ganglio-oligosaccharides added directly to patient sera, without the requirement of antibody fractionation. Both immunoglobulins were found to have similar binding modalities, with interaction confined to two distinct spatially separated regions of GM1: the terminal betaGal(1-3)betaGalNAc disaccharide unit and the sialic acid residue. We describe a unique and powerful biophysical technique applied to define the molecular interaction between autoimmune disease-causing antibodies and their ganglioside targets.
authors.affiliation: Institute for Biological Sciences, National Research Council Canada, Ottawa, Ontario K1A 0R6, Canada.
authors.forename: R Scott
authors.initials: RS
authors.lastname: Houliston
authors.forename: Bart C
authors.initials: BC
authors.lastname: Jacobs
authors.forename: Anne P
authors.initials: AP
authors.lastname: Tio-Gillen
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Verschuuren
authors.forename: Nam H
authors.initials: NH
authors.lastname: Khieu
authors.forename: Michel
authors.initials: M
authors.lastname: Gilbert
authors.forename: Harold C
authors.initials: HC
authors.lastname: Jarrell
mesh_terms: D000906:Antibodies / Q000276:immunology; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D055592:Biophysical Phenomena; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D000939:Epitopes; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011115:Polyneuropathies / Q000175:diagnosis / Q000276:immunology; D012680:Sensitivity and Specificity
chemical_list: D000906:Antibodies; D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D000939:Epitopes; D005732:Gangliosides; D008024:Ligands; C044203:anti-IgM