title: Different IVIG glycoforms affect in vitro inhibition of anti-ganglioside antibody-mediated complement deposition.
abstract: Intravenous immunoglobulin (IVIG) is the first line treatment for Guillain-Barré syndrome and multifocal motor neuropathy, which are caused by anti-ganglioside antibody-mediated complement-dependent cytotoxicity. IVIG has many potential mechanisms of action, and sialylation of the IgG Fc portion reportedly has an anti-inflammatory effect in antibody-dependent cell-mediated cytotoxicity models. We investigated the effects of different IVIG glycoforms on the inhibition of antibody-mediated complement-dependent cytotoxicity. Deglycosylated, degalactosylated, galactosylated and sialylated IgG were prepared from IVIG following treatment with glycosidases and glycosyltransferases. Sera from patients with Guillain-Barré syndrome, Miller Fisher syndrome and multifocal motor neuropathy associated with anti-ganglioside antibodies were used. Inhibition of complement deposition subsequent to IgG or IgM autoantibody binding to ganglioside, GM1 or GQ1b was assessed on microtiter plates. Sialylated and galactosylated IVIGs more effectively inhibited C3 deposition than original IVIG or enzyme-treated IVIGs (agalactosylated and deglycosylated IVIGs). Therefore, sialylated and galactosylated IVIGs may be more effective than conventional IVIG in the treatment of complement-dependent autoimmune diseases.
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sudo
authors.affiliation: Structural Glycobiology Team, RIKEN, Wako, Saitama, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Institute of Pharmacology, University of Bern, Bern, Switzerland.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Späth
authors.affiliation: Structural Glycobiology Team, RIKEN, Wako, Saitama, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Matsumoto-Morita
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Ong
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Nortina
authors.initials: N
authors.lastname: Shahrizaila
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yuki
mesh_terms: D001323:Autoantibodies / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism*; D005732:Gangliosides / Q000037:antagonists & inhibitors / Q000276:immunology*; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D016756:Immunoglobulins, Intravenous / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D011134:Polysaccharides / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D005732:Gangliosides; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D011134:Polysaccharides; D003165:Complement System Proteins