Late onset of development of natural anti-nonGal antibodies in infant humans and baboons: Implications for xenotransplantation in infants
If an ABO-incompatible heart is transplanted into an infant before natural antibodies have developed to the specific donor carbohydrate A/B antigen(s), then B-cell tolerance to the donor A/B antigen is achieved, and these antibodies never develop. Anti-carbohydrate antibodies play a role in the rejection of wild type (WT) and α1,3-galactosyltransferase gene-knockout (GT-KO) pig xenografts. We investigated development of these antibodies in infant baboons and humans. Serum samples from infant baboons (n = 42) and humans (n = 42) were tested by flow cytometry for immunoglobulin M and immunoglobulin G binding to peripheral blood mononuclear cells from WT and GT-KO pigs, and for complement-dependent cytotoxicity. The presence of anti-blood group antibodies was tested in baboon serum. In infant baboons and humans, cytotoxic anti-Galα1,3Gal antibodies develop during the first 3 months, and steadily increase with age, whereas cytotoxic anti-nonGal antibodies are either absent or minimal in the majority of cases throughout the first year of life. Anti-blood group antibodies were not detected before 16 weeks of age. Our data suggest GT-KO pig organ/cell transplants could be carried out in early infancy in the absence of preformed cytotoxic anti-nonGalα1,3Gal antibodies.
|Keywords||Anti-pig antibodies, Infants, Primates, Xenotransplantation, α1,3-galactosyltransferase gene-knockout|
|Persistent URL||dx.doi.org/10.1111/j.1432-2277.2007.00546.x, hdl.handle.net/1765/36358|
Rood, P.P.M., Tai, H.-C., Hara, H., Long, C., Ezzelarab, M., Lin, Y.J., … Cooper, D.K.C.. (2007). Late onset of development of natural anti-nonGal antibodies in infant humans and baboons: Implications for xenotransplantation in infants. Transplant International, 20(12), 1050–1058. doi:10.1111/j.1432-2277.2007.00546.x