Glycobiology Advance Access originally published online on December 4, 2006
Glycobiology 2007 17(3):294-303; doi:10.1093/glycob/cwl074
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Solid phase immunoadsorption for therapeutic and analytical studies on neuropathy-associated anti-GM1 antibodies
2 Division of Clinical Neurosciences
3 Department of Chemistry, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow G12 8TA, UK
4 Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2
5 CERMAV-CNRS, BP53, F-38041, GRENOBLE cedex 9, France
6 Dipartimento di Chimica Organica e Industriale, Universita' degli Studi di Milano, Via Venezian 21, I-20133 Milano, Italy
7 Department of Medical Chemistry, Biochemistry and Biotechnology
8 Center of Excellence on Neurodegenerative Diseases, University of Milan, 20090 Segrate(Mi), Italy
1 To whom correspondence should be addressed; Tel: +44 141 330 8384; Fax: +44 141 330 4297; e-mail: 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 favored 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 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.
Key words: antibody / GM1 ganglioside / immunoadsorption / neuropathy / treatment
Ganglioside nomenclature is in accordance with Svennerholm (1980) and IUPAC-UIBMB recommendations (www.chem.qmul.ac.uk/iupac/misc/glylp.html).
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