Preformed antibodies to alpha1,3-galactosyltransferase gene-knockout (GT-KO) pig cells in humans, baboons, and monkeys: implications for xenotransplantation

Transplant Proc. 2005 Oct;37(8):3514-5. doi: 10.1016/j.transproceed.2005.09.082.

Abstract

Objective: The aim of our study was to determine the prevalence and cytotoxicity of primate antibodies directed to antigens other than Galalpha1,3Gal (Gal), termed nonGal antigens.

Methods: Sera from human, baboon, and cynomolgus monkeys were tested by flow cytometry for IgM and IgG binding to both wild-type (WT) and GT-KO pig peripheral mononuclear cells (PBMC). Also, complement-dependent cytotoxicity assays were performed.

Results: All species demonstrated significantly higher antibody binding and cytotoxicity to WT cells compared to GT-KO cells (P < .01). Cynomolgus monkeys had significantly higher IgM binding to WT and GT-KO cells than did baboons or humans (P < .01). Furthermore, approximately 50% of both human and baboon sera proved to be lytic to GT-KO cells, compared to 76% of monkey sera (P < .01).

Conclusions: We confirm the advantage of using GT-KO pig grafts over WT pig grafts. However, our results suggest that, compared to the cynomolgus monkey, the baboon may be a more suitable model to study antibody-mediated rejection of GT-KO pig grafts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Heterophile / blood
  • Cytotoxicity, Immunologic
  • Galactosyltransferases / deficiency*
  • Galactosyltransferases / immunology*
  • Gene Deletion*
  • Graft Rejection / microbiology
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Islets of Langerhans Transplantation / immunology
  • Leukocytes, Mononuclear / immunology
  • Macaca fascicularis
  • Papio
  • Swine

Substances

  • Antibodies, Heterophile
  • Immunoglobulin G
  • Immunoglobulin M
  • Galactosyltransferases
  • alpha 1,3 galactosyltransferase, mouse