Specific binding of intravenous immunoglobulin products to tau peptide fragments

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. Antibody concentrations to tau 45–73 and 422–441 were significantly higher in Gamunex than Gammagard and Flebogamma. There were no differences between their antibody concentrations to the four microtubule binding domains. [Display omitted] •Three IVIG products were compared for antibody binding to six tau fragments.•Antibodies to N- and C-terminal tau fragments differed between IVIG products.•Patterns of binding to the tau fragments also differed between IVIG products.•These could result in differences in IVIG products' effects on tau neurotoxicity.