Anti-N-glycolylneuraminic acid antibodies identified in healthy human serum

The first and major clinical obstacle in xenotransplantation is antibody-mediated hyperacute rejection. Although human natural antibodies against Galalpha1,3Gal (Gal) antigens, which are common on porcine cells and organs, have been identified to play a major role in hyperacute rejection, other natural antibodies against non-Gal epitopes may be also involved in the process. Here, we present evidence suggesting that the majority of human anti-non-Gal antibodies are specific for carbohydrate structures carrying terminally linked N-glycolylneuraminic acid (NeuGc), a xenoantigen existing in almost all animals except humans. Furthermore, this anti-NeuGc activity is detectable in 85% of healthy humans, implicating the involvement of NeuGc in hyperacute rejection and the importance of developing strategies for removing NeuGc for clinical xenotransplantation.