Antibodies directed to pig non-Gal antigens in naïve and sensitized baboons.
BACKGROUND
As pigs homozygous for alpha1,3-galactosyltransferase gene-knockout (GT-KO) are available, primate antibodies to pig non-Gal antigens can be studied.


METHODS
Sera from 56 baboons were tested for binding of IgM and IgG to peripheral blood mononuclear cells (PBMC) from both wild-type (WT) and GT-KO pigs by flow cytometry. Complement-dependent cytotoxicity was measured in 39 sera. Antibody and cytotoxicity responses were measured in two baboons exposed to a GT-KO pig heart, one not immunosuppressed and one that received only cobra venom factor.


RESULTS
IgM and IgG bound to 95% and 79% of WT PBMC, and 32% and 9% GT-KO PBMC, respectively (WT vs. GT-KO, P<0.01). Whereas 97% of sera were cytotoxic to WT PBMC, only 64% were cytotoxic to GT-KO PBMC, and the level of cytotoxicity was less (mean 60% vs. 25% lysis, P<0.05). In the two baboons exposed to GT-KO hearts, anti-non-Gal antibodies increased markedly, peaking after 2 (IgM) and 3 (IgG) weeks, associated with an increase in lysis of GT-KO PBMC.


CONCLUSIONS
Two-thirds of baboon sera demonstrated cytotoxicity to GT-KO PBMC. After GT-KO organ transplantation, if an elicited antibody response develops, it is likely to cause rapid graft rejection.
Ezzelarab
Mohamed
M
Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
Hara
Hidetaka
H
Busch
Jamie
J
Rood
Pleunie P M
PP
Zhu
Xiaocheng
X
Ibrahim
Zuhaib
Z
Ball
Suyapa
S
Ayares
David
D
Awwad
Michel
M
Cooper
David K C
DK
D000818:Animals; D000906:Antibodies / Q000032:analysis*; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D005700:Galactosyltransferases / Q000235:genetics* / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D048530:Papio anubis / Q000276:immunology*; D048529:Papio hamadryas / Q000276:immunology*; D013552:Swine / Q000276:immunology*; D014183:Transplantation, Heterologous
D000906:Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D003165:Complement System Proteins; D005700:Galactosyltransferases