Effect of human immunoglobulins on the immunogenicity of porcine bioprostheses

Abstract Background . Glutaraldehyde fixation (GT) is known to reduce immunologic reactions and tissue degeneration after implantation in humans. Sterilization after glutaraldehyde fixation (G-ST) improves the safety and reduces the tendency of GT valves to calcify. Intravenous immunoglobulins (IVIg) have been shown to reduce xenogeneic response against porcine tissue. We have investigated the effect of these fixation procedures combined with and without IVIg on the antigenicity of bioprostheses. Methods . Lewis adult rats were implanted subcutaneously with a fresh, GT, or G-ST porcine heart valve pre- or posttreated with different amounts of IVIg. We followed by enzyme-linked immunosorbent assay and IgM and IgG titers against protein extracts from the porcine heart valves after implantation. Cellular reactivity was assessed in xenogeneic lymphoendothelial coculture experiments. Calcification content was also examined. Results . Glutaraldehyde fixation partially decreased the humoral response against proteins of the implant but elicited a cellular xenogeneic response. Sterilization reduced these reactivities, but retained antigenicity. Intravenous immunoglobulin postincubated with GT valves before implantation reduced the antigenicity of the tissue to the same extent as G-ST valves, but had no effect on valvular tissue calcification. Conclusions . Our studies demonstrate that IVIg or the sterilization procedure (ST) reduced the cellular response against glutaraldehyde-fixed valves (GT), whereas reduced calcification was observed only with ST.