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

Abstract: The first and major clinical obstacle in xenotransplantation is antibody‐mediated hyperacute rejection. Although human natural antibodies against Galα1,3Gal (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.