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 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.

Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid

“…While this article was in preparation, another group independently reported a high prevalence of anti-Neu5Gc antibodies in normal human sera, using a different approach (39). The findings of both studies stand in contrast to previous reports of the prevalence of anti-Neu5Gc antibodies in normal humans, ranging only from 0-10% for the IgG class to 3.8-13.8% for the IgM class (40)(41)(42).…”

Thrombotic Microangiopathy Associated with Humoral Rejection of Cardiac Xenografts from α1,3-Galactosyltransferase Gene-Knockout Pigs in Baboons

“…Recently, several reports have suggested that the possible epitopes on pig grafts recognized by human non-Gal antibodies include swine leukocyte antigen, N-glycolylneuraminic acid (NeuGc) epitopes (Hanganutziu-Deicher antigen, although this would not be a target in baboons because these animals also express this antigen), and Forssman antigen. 30,33,34 Further experiments are necessary to clarify the novel target epitope of non-Gal antibodies to consider other strategies to prevent non-Gal antibody-mediated rejection, including the deletion or modification of non-Gal epitopes by genetic engineering of the pig.…”

Effects of Natural Human Antibodies against a Nonhuman Sialic Acid That Metabolically Incorporates into Activated and Malignant Immune Cells

“…The total levels of IgG varied widely among individuals. Similarly, others found that 85% of healthy human subjects had anti-Neu5Gc Ig activity (29). The significance of such anti-Neu5Gc Abs in apparently healthy humans remains unknown, and their functional capabilities have not been demonstrated.…”