Preformed antibodies to alpha1,3-galactosyltransferase gene-knockout (GT-KO) pig cells in humans, baboons, and monkeys: implications for xenotransplantation.
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.
Rood
P P M
PP
Starzl Transplantation Institute, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15261, USA.
Hara
H
H
Ezzelarab
M
M
Busch
J
J
Zhu
X
X
Ibrahim
Z
Z
Ball
S
S
Ayares
D
D
Awwad
M
M
Cooper
D K C
DK
D000818:Animals; D000910:Antibodies, Heterophile / Q000097:blood; D003602:Cytotoxicity, Immunologic; D005700:Galactosyltransferases / Q000172:deficiency* / Q000276:immunology*; D017353:Gene Deletion; D006084:Graft Rejection / Q000382:microbiology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D016381:Islets of Langerhans Transplantation / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008252:Macaca fascicularis; D010215:Papio; D013552:Swine
D000910:Antibodies, Heterophile; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D005700:Galactosyltransferases; C487611:alpha 1,3 galactosyltransferase, mouse