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

Publication/Presentation Date

10-1-2005

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.

Volume

37

Issue

8

First Page

3514

Last Page

3515

ISSN

0041-1345

Disciplines

Medicine and Health Sciences

PubMedID

16298646

Department(s)

Department of Surgery

Document Type

Article

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