Late onset of development of natural anti-nonGal antibodies in infant humans and baboons: implications for xenotransplantation in infants

Authors


David K. C. Cooper MD, PhD, FRCS, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Starzl Biomedical Science Tower W1540, 200 Lothrop Street, Pittsburgh, PA 15261, USA. Tel.: +1 412 383 6961; fax: +1 412 624 6666;
e-mail: cooperdk@upmc.edu

Summary

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 (= 42) and humans (= 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.

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