title: Detection of antibodies in neuropathy patients by synthetic GM1 mimics.
abstract: Antibodies to the ganglioside GM1 are associated with various forms of acute and chronic immune-mediated neuropathy, including Guillain-Barré syndrome (GBS) and multifocal motor neuropathy. In diagnostics and research, these antibodies are usually detected by GM1 preparations derived from bovine brain tissue, which are non-covalently attached to solid carriers such as enzyme-linked immunosorbent assay (ELISA) plates. Such brain-derived GM1 preparations are potentially contaminated with other glycolipids. In the current study, uncontaminated mono- and divalent synthetic analogs of the ganglioside GM1 were successfully attached via covalent bonds onto the surface of ELISA plates. The resulting modified diagnostic tool showed strong affinities and good specificities for binding of monoclonal mouse and human anti-GM1 antibodies and cholera toxin, as well as for the anti-GM1 antibodies in serum samples from neuropathy patients. While these proof-of-principle experiments reveal the potential of synthetic ganglioside mimics in diagnostics, they show the necessity of further studies to overcome certain limitations, specifically the non-specific interactions in the negative control assays with synthetic GM1.
authors.affiliation: Laboratory of Organic Chemistry, Wageningen University, Dreijenplein 8, 6703 HB Wageningen, The Netherlands.
authors.forename: Aliaksei V
authors.initials: AV
authors.lastname: Pukin
authors.forename: Bart C
authors.initials: BC
authors.lastname: Jacobs
authors.forename: Anne P
authors.initials: AP
authors.lastname: Tio-Gillen
authors.forename: Michel
authors.initials: M
authors.lastname: Gilbert
authors.forename: Hubert P
authors.initials: HP
authors.lastname: Endtz
authors.forename: Alex
authors.initials: A
authors.lastname: van Belkum
authors.forename: Gerben M
authors.initials: GM
authors.lastname: Visser
authors.forename: Han
authors.initials: H
authors.lastname: Zuilhof
mesh_terms: D000911:Antibodies, Monoclonal / Q000097:blood* / Q000276:immunology*; D005677:G(M1) Ganglioside / Q000737:chemistry* / Q000276:immunology; D020275:Guillain-Barre Syndrome / Q000097:blood / Q000276:immunology*; D006801:Humans; D018716:Molecular Mimicry; D010265:Paraproteinemias / Q000097:blood / Q000276:immunology*; D011115:Polyneuropathies / Q000097:blood / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D005677:G(M1) Ganglioside