title: Solid phase immunoadsorption for therapeutic and analytical studies on neuropathy-associated anti-GM1 antibodies.
abstract: Autoimmune neuropathies including Guillain-Barré syndrome are frequently associated with anti-GM1 ganglioside antibodies. These are believed to play a pathogenic role and their clearance from the circulation would be predicted to produce therapeutic benefit. This study examines the conditions required for effective immunoadsorption of anti-GM1 antibodies using glycan-conjugated Sepharose as a matrix. In solution inhibition studies using a range of GM1-like saccharides in conjunction with mouse and human anti-GM1 antibodies, the whole GM1 pentasaccharide beta-Gal-(1-3)-beta-GalNAc-(1-4)-[alpha-Neu5Ac-(2-3)]-beta-Gal-(1-4)-beta-Glc was the favored ligand for maximal inhibiton of antibody-GM1 interactions in comparison with monosaccharides, Gal-(1-3)-beta-GalNAc-betaOMe, and synthetic GM1 mimetics. Immunoadsorption studies comparing binding of mouse monoclonal anti-GM1 antibodies to GM1-Sepharose and beta-Gal-(1-3)-beta-GalNAc-Sepharose confirmed the preference seen in solution inhibition studies. GM1-Sepharose columns were then used to adsorb anti-GM1 immunoglobulin G and immunoglobulin M antibodies from human neuropathy sera. Anti-GM1 antibodies subsequently eluted from the columns often showed a striking monoclonal or oligoclonal pattern, indicating that the immune response to GM1 is restricted to a limited number of B-cell clones, even in the absence of a detectable serum paraprotein. These data support the view that immunoadsorption plasmapheresis could potentially be developed for the acute depletion of serum anti-GM1 antibodies in patients with neuropathic disease, and also provide purified human anti-GM1 antibodies for analytical studies.
authors.affiliation: Division of Clinical Neurosciences, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Townson
authors.forename: Judith
authors.initials: J
authors.lastname: Boffey
authors.forename: Dawn
authors.initials: D
authors.lastname: Nicholl
authors.forename: Jean
authors.initials: J
authors.lastname: Veitch
authors.forename: David
authors.initials: D
authors.lastname: Bundle
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Eric
authors.initials: E
authors.lastname: Samain
authors.forename: Tatiana
authors.initials: T
authors.lastname: Antoine
authors.forename: Anna
authors.initials: A
authors.lastname: Bernardi
authors.forename: Daniela
authors.initials: D
authors.lastname: Arosio
authors.forename: Sandro
authors.initials: S
authors.lastname: Sonnino
authors.forename: Neil
authors.initials: N
authors.lastname: Isaacs
authors.forename: Hugh J
authors.initials: HJ
authors.lastname: Willison
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology / Q000302:isolation & purification*; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology* / Q000628:therapy*; D005677:G(M1) Ganglioside / Q000276:immunology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009844:Oligosaccharides / Q000276:immunology; D010956:Plasmapheresis / Q000379:methods*; D016060:Sorption Detoxification / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; C519498:GM1 pentasaccharide; D009844:Oligosaccharides; D005677:G(M1) Ganglioside