Solid phase immunoadsorption for therapeutic and analytical studies on neuropathy-associated anti-GM1 antibodies
Autor(es): Townson Kate,Boffey Judith,Nicholl Dawn,Veitch Jean,Bundle David,Zhang Ping,Samain Eric,Antoine Tatiana,Bernardi Anna,Arosio Daniela,Sonnino Sandro,Isaacs Neil,Willison Hugh J
Resumo: 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.
Palavras-Chave: Antibody; GM1 ganglioside; Immunoadsorption; Neuropathy; Treatment
Imprenta: Glycobiology, v. 17, n. 3, p. 294-303, 2007
Identificador do objeto digital: 10.1093/glycob/cwl074
Descritores: Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - Immune response ; Guillain-Barre Syndrome - Pathogenesis ; Guillain-Barre Syndrome - Proteins ; Guillain-Barre Syndrome - Antibodies ; Guillain-Barre Syndrome - Immunology
Data de publicação: 2007
