Newborn baboon immunity: Lessons in cross-species transplantation

Background: The critical shortage of organ donors has greatly limited the number of heart transplantations performed each year. This is particularly true of the newborn patient, for whom xenotransplantation may provide an alternative therapeutic option to allotransplantation. The role of newborn immunity in xenotransplantation is not clearly understood. Methods: We examined the humoral immune responses of 9 nonimmunosuppressed newborn baboons (900 to 1200 g) aged 28 to 44 days undergoing heterotopic pig heart transplantation. Grafts were explanted between 1 and 87 hours after transplantation. Results: Despite the degree of species disparity, hyperacute rejection was not observed in any of the nine transplanted grafts. Whole-cell enzyme-linked immunosorbent assay demonstrated newborn baboon serum to contain very low binding levels of anti-pig natural immunoglobulin M xenoantibody when compared with adult baboon serum. Newborn baboon serum, like adult serum, contained anti-pig natural immunoglobulin G xenoantibody. However, newborn baboon serum was not cytotoxic to pig endothelial cells, suggesting that immunoglobulin M and not immunoglobulin G is the primary xenoreactive antibody. Conclusions: The low binding levels of anti-pig immunoglobulin M xenoantibody, the absence of cytotoxicity to pig endothelial cells, and the avoidance of hyperacute rejection after heart transplantation suggest that new-born primates may have an immunologic advantage as the recipients of hearts transplanted across species barriers. Whether this advantage can be extended to the human condition is currently being explored in our laboratory.