Glycobiology Advance Access published online on December 4, 2006
Glycobiology, doi:10.1093/glycob/cwl074
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Solid phase immunoadsorption for therapeutic and analytical studies on neuropathy-associated anti-GM1 antibodies
1 Division of Clinical Neurosciences University of Glasgow, Scotland G12 8TA
2 Department of Chemistry, Glasgow Biomedical Research Centre, University of Glasgow, Scotland G12 8TA
3 Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2
4 CERMAV-CNRS, BP53, F-38041, GRENOBLE, cedex 9, France
5 Dipartimento di Chimica Organica e Industriale, Universita' degli Studi di Milano, Via Venezian 21, I-20133 Milano, Italy
6 Department of Medical Chemistry, Biochemistry and Biotechnology, and Center of Excellence on Neurodegenerative Diseases, University of Milan, 20090 Segrate(Mi), Italy
Correspondence: Professor Hugh J Willison, Division of Clinical Neurosciences, Room B330, Glasgow Biomedical Research Centre, University of Glasgow, Scotland G12 8TA Tel: 44 141 330 8384; Fax: 44 141 330 4297; email: h.j.willison{at}clinmed.gla.ac.uk
Received on June 28, 2006; revised on October 30, 2006; accepted on November 22, 2006
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, ß-Gal-(1-3)-ß-GalNAc-(1-4)-[
-Neu5Ac-(2-3)]-ß-Gal-(1-4)-ß-Glc, was the favoured ligand for maximal inhibiton of antibody-GM1 interactions in comparison with monosaccharides, Gal-(1-3)-ß-GalNAc-ßOMe, and synthetic GM1 mimetics. Immunoadsorption studies comparing binding of mouse monoclonal anti-GM1 antibodies to GM1-Sepharose and ß-Gal-(1-3)-ß-GalNAc-Sepharose confirmed the preference seen in solution inhibition studies. GM1-Sepharose columns were then used to adsorb anti-GM1 IgG and IgM 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.
Key words: antibody / GM1 ganglioside / immunoadsorption/neuropathy / treatment
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