title: Anti-GM1/GD1a complex antibodies in GBS sera specifically recognize the hybrid dimer GM1-GD1a.
abstract: It is now emerging the new concept that the antibodies from some patients with Guillain-Barré syndrome (GBS) recognize an antigenic epitope formed by two different gangliosides, a ganglioside complex (GSC). We prepared the dimeric GM1-GD1a hybrid ganglioside derivative that contains two structurally different oligosaccharide chains to mimic the GSC. We use this compound to analyze sera from GBS patients by high-performance thin-layer chromatography immunostaining and enzyme-linked immunosorbent assay. We also synthesized the dimeric GM1-GM1 and GD1a-GD1a compounds that were used in control experiments together with natural gangliosides. The hybrid dimeric GM1-GD1a was specifically recognized by human sera from GBS patients that developed anti-oligosaccharide antibodies specific for grouped complex oligosaccharides, confirming the information that GBS patients developed antibodies against a GSC. High-resolution (1)H-(13)C heteronuclear single-quantum coherence-nuclear overhauser effect spectroscopy nuclear magnetic resonance experiments showed an interaction between the IV Gal-H1 of GM1 and the IV Gal-H2 of GD1a suggesting that the two oligosaccharide chains of the dimeric ganglioside form a single epitope recognized by a single-antibody domain. The availability of a method capable to prepare several hybrid gangliosides, and the availability of simple analytical approaches, opens new perspectives for the understanding and the therapy of several neuropathies.
authors.affiliation: Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, Via Fratelli Cervi 93, 20090 Segrate, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Mauri
authors.forename: Riccardo
authors.initials: R
authors.lastname: Casellato
authors.forename: Maria G
authors.initials: MG
authors.lastname: Ciampa
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Uekusa
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Kaida
authors.forename: Mayumi
authors.initials: M
authors.lastname: Motoyama
authors.forename: Susumu
authors.initials: S
authors.lastname: Kusunoki
authors.forename: Sandro
authors.initials: S
authors.lastname: Sonnino
mesh_terms: D001324:Autoantigens / Q000737:chemistry / Q000276:immunology; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002855:Chromatography, Thin Layer; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005677:G(M1) Ganglioside / Q000737:chemistry / Q000276:immunology*; D005732:Gangliosides / Q000737:chemistry / Q000276:immunology*; D020275:Guillain-Barre Syndrome / Q000097:blood* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000737:chemistry; D008969:Molecular Sequence Data; D009844:Oligosaccharides; D025942:Oligosaccharides, Branched-Chain / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding; D044967:Serum
chemical_list: D001324:Autoantigens; D000939:Epitopes; D005732:Gangliosides; D007074:Immunoglobulin G; D009844:Oligosaccharides; D025942:Oligosaccharides, Branched-Chain; C021298:ganglioside, GD1a; D005677:G(M1) Ganglioside