Anti-pig antibody levels in non-human primates of various origin

Background: Natural anti-porcine antibodies play a major role in hyperacute solid organ xenograft rejection in the pig-to-non-human primate model. Work from other groups and our experience in transplantation experiments has shown that antibody levels are highly variable between non-human primate species, and that extremely high levels can mediate hyperacute rejection even if organs from animals transgenic for human decay-accelerating factor are used. Methods: Sera were obtained from cynomolgus monkeys wild-caught in Mauritius, captive-bred in the Philippines, captive-bred in Indonesia (Indonesia-Ind), and originating from Indonesia but colony-bred in USA (Indonesia-USA), from baboons wild-caught in Kenya, and from rhesus monkeys originating from India but colony-bred in USA (10 animals in each group). Antibody levels were determined using assays for haemolytic antibody (APA), IgM and IgG class anti-Galα1-3Gal antibody, and IgM and IgG class anti-endothelial cell antibody. Results: Cynomolgus monkeys from the Philippines and Indonesia-USA and rhesus monkeys showed median APA and IgM antibody levels in the same range as a pooled human serum standard, and median IgG levels well below the level in this standard. Cynomolgus monkeys from Mauritius and Indonesia-Ind showed extremely high APA levels (median seven to 10 times the human serum standard): IgM class antibodies were also higher, while IgG class antibodies were in the range of the level in the human serum standard. Antibody levels in baboons were in between these two categories. The results of the APA assay showed a highly statistically significant correlation with the assays of IgM antibody, and this was also the case for the IgM antibody assays, indicative of the assessment of the same antibodies in these assays. The same was observed for the assays for IgG antibody. Taking body weight as an indicator for age, there was no relationship between body weight and levels of antibodies. Conclusions: Natural antibody levels show a significant variation between various groups of non-human primates, with levels in some groups well above those in a human serum standard.