Present address: Department of Medicine, University of Manitoba, Winnipeg, MB, Canada.
Late onset of development of natural anti-nonGal antibodies in infant humans and baboons: implications for xenotransplantation in infants
Article first published online: 10 SEP 2007
Volume 20, Issue 12, pages 1050–1058, December 2007
How to Cite
Rood, P. P. M., Tai, H.-C., Hara, H., Long, C., Ezzelarab, M., Lin, Y. J., Van Der Windt, D. J., Busch, J., Ayares, D., Ijzermans, J. N. M., Wolf, R. F., Manji, R., Bailey, L. and 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: 1050–1058. doi: 10.1111/j.1432-2277.2007.00546.x
- Issue published online: 10 SEP 2007
- Article first published online: 10 SEP 2007
- Received: 17 May 2007 Revision requested: 12 June 2007 Accepted: 28 July 2007
- α1,3-galactosyltransferase gene-knockout;
- anti-pig antibodies;
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.