Variation in expression of porcine xenogeneic antigens

The rejection of organs transplanted between phylogenetically disparate animals such as pigs and primates is thought to be initiated by binding of naturally occurring antibodies of the recipient to blood vessels in the donor organ. The major porcine target antigens are a triad of glycoproteins, gp115/135, which are expressed on endothelial cells and platelets of all animals tested to date. Whether expression of these antigens varies to the extent that selection of particular animals as donors for xenotransplantation would be warranted is an important question that has not been addressed previously. We tested the reactivity of human natural antibodies with platelet-derived antigens isolated from > 60 pigs representing 4 strains. Reactivity with IgM from a single human serum sample varied to such an extent as to suggest a 5-fold difference in the levels of antigen expression. Significantly, approximately 10% of animals express very low levels of the target antigens. The variations in antigen levels were not due to the age or sex of the animal or to environmental effects. There appears to be genetic regulation of the expression, as sibling pairs were more likely to have similar levels of reactivity than nonsiblings. Western blotting of platelet extracts shows the same quantitative differences in expression of the individual glycoproteins gp115, 125, and 135 as is seen by ELISA for all xenogeneic antigens. The levels of expression of gp115/135 appear to be controlled coordinately and are consistent with genetic regulation. While the clinical relevance of these observations is unclear, it is possible that lower levels of expression of these antigens on donor organs might lead to enhanced xenograft survival. In addition, in the experimental situation, the outcome of particular experiments might be affected by the selection of particular donor-recipient pairs.