title: Specific binding of intravenous immunoglobulin products to tau peptide fragments.
abstract: The effects of intravenous immunoglobulin (IVIG) products are being evaluated in Alzheimer's disease (AD) patients. IVIG contains antibodies to tau protein, the main constituent of neurofibrillary tangles (NFTs). Tau has microtubule binding domain (MBD) repeats which are thought to be necessary for its aggregation, a key process in NFT formation. Tau's N-terminal region may also contribute to its aggregation and to the neurotoxicity of its soluble oligomers. This study examined the specific binding of IVIG products Gammagard, Gamunex, and Flebogamma to a tau N-terminal fragment (tau 45-73), tau's four MBD repeat sequences (tau 244-274, 275-305, 306-336, and 337-368), and a tau C-terminal fragment (tau 422-441). Mean antibody levels to tau 45-73 and tau 422-441 were significantly higher in Gamunex than in Gammagard and Flebogamma, while there were no significant differences between IVIG products for antibody concentrations to the MBD repeat sequences. Patterns of binding to tau fragments differed between IVIG products. Gammagard's highest binding was to tau 275-305 and tau 306-336 while Gamunex bound preferentially to tau 45-73 and tau 422-441. Flebogamma's binding to tau 275-305 and tau 306-336 was greater than to tau 337-368, and its binding to tau 306-336 was also higher than to tau 422-441. These findings indicate that IVIG products vary with respect to their binding to different regions of tau. This could result in differences with regard to their ability to prevent tau's aggregation and/or tau soluble oligomer neurotoxicity.
authors.affiliation: Department of Neurology Research, Beaumont Health System, 3811 West Thirteen Mile Road, Royal Oak, MI 48073, USA.
authors.forename: Lynnae M
authors.initials: LM
authors.lastname: Smith
authors.affiliation: Department of Biostatistics, Beaumont Research Institute, Beaumont Health System, 3811 West Thirteen Mile Road, Royal Oak, MI 48073, USA.
authors.forename: Mary P
authors.initials: MP
authors.lastname: Coffey
authors.affiliation: Department of Neurology Research, Beaumont Health System, 3811 West Thirteen Mile Road, Royal Oak, MI 48073, USA. Electronic address: DLoeffler@beaumont.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Loeffler
mesh_terms: D000906:Antibodies / Q000276:immunology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology*; D016875:tau Proteins / Q000276:immunology*
chemical_list: D000906:Antibodies; D016756:Immunoglobulins, Intravenous; D010446:Peptide Fragments; D016875:tau Proteins
keywords: Alzheimer's disease; Antibody binding; ELISA; IVIG; Intravenous immunoglobulin; Tau