Does exposure to swine leukocyte antigens after pig-to-nonhuman primate xenotransplantation provoke antibodies that cross-react with human leukocyte antigens?

: Background: A potential concern of using pig kidney xenografts for human transplantation is that antibodies produced to swine leukocyte antigens (SLA) may cross‐react with human leukocyte antigens (HLA) and thereby limit the scope for a subsequent human organ donor transplant. We therefore investigated whether exposure to SLA after pig‐to‐nonhuman primate kidney xenotransplantation gives rise to HLA cross‐reactive antibodies. Methods: Serum samples were obtained from 52 cynomolgus monkeys that received kidney transplants from human decay‐accelerating factor (hDAF) transgenic pigs. Samples were collected pre‐transplant and at time of autopsy (mean 20 days post‐transplantation, range 1 to 53 days) and analyzed for IgG HLA class I and HLA class II specific antibodies by enzyme‐linked immunosorbent assay (ELISA) against pooled purified HLA antigens. To ensure the ability of the HLA ELISA to detect cynomolgus monkey IgG binding, parallel experiments were performed to detect IgG Gal‐α‐1,3‐Gal‐specific antibodies known to be present in cynomolgus monkey serum. Results: Analysis of both pre‐ and post‐transplantation serum samples by ELISA demonstrated no detectable IgG antibody binding to HLA class I or class II antigens. Using the same ELISA antibody detection reagents, IgG Gal‐α‐1,3‐Gal‐specific antibodies were identified in 13 of 38 (34%) sera obtained before transplantation and 21 of 52 (40%) sera collected post‐transplantation, confirming that the negativeHLA ELISA results were not due to a technical aspect of the assay. Conclusion: This study suggests that exposure to SLA following transplantation of porcine kidneys in nonhuman primates does not give rise to antibodies that cross‐react with HLA.