Utility of xenografts: Lack of correlation between PRA and natural antibodies to swine

Among the patients that might potentially benefit from the availability of xenografts are those in kidney failure who demonstrate high levels of antibody reactivity to panels of typing lymphocytes. Such individuals with high PRA (panel reactive antibody) are unlikely to receive a renal allograft because they are highly sensitized to the vast majority of potential donors. In addition, all humans have demonstrable levels of natural antibodies reactive to distantly related species such as the pig. If there were a correlation between PRA and levels of natural antibodies, then such patients would also be at greater risk for hyperacute rejection of xenografts. We have therefore examined, in a blinded fashion, the porcine lymphocyte reactivity of sera from PRA positive donors. Subsets of the 105 sera tested were grouped by PRA level and analyzed for levels of natural antibodies detectable by a complement-dependent cytotoxicity assay on porcine lymphocytes. There was no significant difference in the range of titers of natural antibodies between subsets. Thus, there was no demonstrable correlation between levels of PRA and levels of natural antibodies to porcine lymphocytes. In addition, we studied the sera of 11 highly sensitized patients who received renal allografts and conventional triple drug immunosuppression in order to determine whether immunosuppression to maintain a vascularized allograft had an effect on PRA and/or xenoreactivity. Mean post-operative PRA was significantly lower than mean pre-operative PRA, while there was no significant difference in xenoreactivity. Thus, pretransplant immunosuppression may permit an increased opportunity to identify compatible human donors for highly sensitized recipients and will not help or hinder the pre-transplant conditioning of a candidate for xenotransplantation.