title: Effect of IVIG Formulation on IgG Binding to Self- and Exo- Antigens In Vitro and In Vivo.
abstract: In relation to the recent trials of Intravenous Immunoglobulin (IVIG) in Alzheimer's Disease (AD) it was demonstrated that different IgG preparations contain varying amounts of natural anti-amyloid β (Aβ) antibodies as measured by ELISA. We therefore investigated the relevance of ELISA data for measuring low-affinity antibodies, such as anti-Aβ. We analysed the binding of different commercial Immunoglobulin G (IgG) preparations to Aβ, actin and tetanus toxoid in different binding assays to further investigate the possible cause for observed differences in binding to Aβ and actin between different IgG preparations. We show that the differences of commercial IgG preparations in binding to Aβ and actin in ELISA assays are artefactual and only evident in in vitro binding assays. In functional assays and in vivo animal studies the different IVIG preparations exhibited very similar potency. ELISA data alone are not appropriate to analyse and rank the binding capacity of low-affinity antibodies to Aβ or other endogenous self-antigens contained in IgG preparations. Additional analytical methods should be adopted to complement ELISA data.
authors: CSL Behring AG, Bern, Switzerland.
authors: Susann
authors: S
authors: Cattepoel
authors: CSL Behring AG, Bern, Switzerland.
authors: Annette
authors: A
authors: Gaida
authors: CSL Behring AG, Bern, Switzerland.
authors: Alain
authors: A
authors: Kropf
authors: CSL Behring GmbH, Marburg, Germany.
authors: Marc W
authors: MW
authors: Nolte
authors: CSL Behring AG, Bern, Switzerland.
authors: Reinhard
authors: R
authors: Bolli
authors: CSL Behring AG, Bern, Switzerland.
authors: Sylvia M
authors: SM
authors: Miescher
mesh_terms: D000199:Actins / Q000276:immunology / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000915:Antibody Affinity / Q000187:drug effects / Q000276:immunology; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D014645:Herpesvirus 3, Human / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D016756:Immunoglobulins, Intravenous / Q000276:immunology* / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D051381:Rats; D013745:Tetanus Toxoid / Q000276:immunology / Q000378:metabolism
chemical_list: D000199:Actins; D016229:Amyloid beta-Peptides; D000941:Antigens; D001324:Autoantigens; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D010446:Peptide Fragments; D013745:Tetanus Toxoid; C075222:amyloid beta-protein (1-42)