Lack of antibody production against Hanganutziu-Deicher (H-D) antigens with N-glycolylneuraminic acid in patients with porcine exposure history

The significance of non-alpha galactosyl antigens remains unclear in pig-to -primate xenotransplantation. Hanganutziu-Deicher (H-D) antigens with termi nal N-glycolylneuraminic acid (NeuGc) are widely expressed on endothelial c ells of mammalian species, with the exception of humans. As baboons and mon keys also express H-D antigens, a pig-to-non-human primate experimental mod el cannot resolve the question of whether H-D antigens can elicit a potent humoral response in human recipients. The purpose of this study was to eluc idate the clinical significance of H-D antigens by examining the sera from patients who have been previously exposed to porcine tissue. After the digestion of porcine aortic endothelial cells (PAEC) by neuramini dase, NeuGc and N-acetylneuraminic acid (NeuAc) were quantitated by HPLC. I gG and IgM antibody levels against H-D antigens were measured by NeuGc-GM3- coated ELISA plates in the sera of patients who had undergone ex vivo kidne y perfusion 1 to 3 weeks and 2 years previously (n=2) or had been injected with fetal porcine islets 2 months previously(n=10). HPLC determined that 9.7x10(7) NeuAc and 6.3x10(7) NeuGc residues per cell were released from PAEC by neuraminidase, while 25.7x10(7) NeuAc and an und etectable level of NeuGc were released from human aortic endothelial cells (HAEC). No significant elevation of IgG or IgM antibody levels against NeuG c-GM3 was observed in sera from patients with a history of porcine exposure . Considering the active production of antibody against the foreign galactosy l antigens after pig-to-human xenotransplantation, some production of antib odies against the equally foreign H-D antigens would be expected, because l arge amounts of NeuGe terminated saccharides are present in the pig endothe lial cell surface. However, no production of antibodies directed to H-D ant igens could be found in patients exposed to porcine tissue. Further studies are warranted to explain why H-D antigens do not elicit a significant anti body production.