Variability of anti‐αGal antibodies in human serum and their relation to serum cytotoxicity against pig cells

Abstract

Abstract: One of the major obstacles in pig‐to‐human xenografting is hyperacute rejection (HAR) of pig cells caused by preformed anti‐pig antibodies and complement. In 1991 we suggested that anti‐αGal antibodies play a major role in the HAR of pig cells. Anti‐αGal antibodies recognize terminal α‐galactose‐containing epitopes on glycoproteins and glycolipids. They are present in humans, apes, and Old World monkeys, but not in lower mammals such as pigs. However, pigs, unlike humans, express terminal α‐galactose epitopes on vascular endothelium which represent targets for human anti‐αGal antibodies. Despite increasing recognition that anti‐αGal antibodies are an important factor, many questions related to their precise role in HAR remain to be answered.In this study, we analyzed 75 human AB sera in terms of (i) cytotoxic activity against cultured pig (PK‐15) cells, (ii) anti‐αGal titers, (iii) immunoglobulin‐binding to pig cells, and (iv) immunoglobulin concentrations. The results demonstrated considerable variability in cytotoxicity, anti‐αGal titers, and immunoglobulin binding to pig cells, whereas the serum immunoglobulin concentrations were less variable. Positive correlations were found between cytotoxicity and binding of IgG and IgM to the surface of pig cells. The surface‐bound IgG and IgM also correlated with the serum anti‐αGal IgG and IgM titers. Anti‐αGal IgA, however, did not show any relation with cytotoxicity or cell binding. Concentrations of serum total immunoglobulins correlated with neither I cytotoxic activity nor cell binding.