Allosensitized humans are at no greater risk of humoral rejection of GT-KO pig organs than other humans.
BACKGROUND
The availability of pigs homozygous for alpha1,3-galactosyltransferase gene-knockout (GT-KO) has enabled study of the incidence and cytotoxicity of primate antibodies directed to antigens other than Galalpha1,3Gal (Gal), termed non-Gal antigens.


METHODS
Sera from 27 healthy humans and 31 patients awaiting renal allotransplantation, who were either unsensitized [panel reactive antibodies (PRA) < 10%] or allosensitized (PRA > 70%), were tested by flow cytometry for binding of immunoglobulin M (IgM) and IgG to peripheral blood mononuclear cells (PBMC) from both wild-type (WT) and GT-KO pigs. Complement-dependent cytotoxicity to WT and GT-KO PBMC was also measured.


RESULTS
IgM and IgG from all 27 (100%) healthy human sera bound to WT PBMC, while 78% and 63% of these sera had IgM and IgG that bound to GT-KO PBMC, respectively. Mean binding to WT PBMC was significantly greater than GT-KO PBMC. Whereas 100% of sera were cytotoxic to WT PBMC, only 61% were cytotoxic to GT-KO PBMC, and the extent of lysis was significantly less. Neither mean binding of IgM and IgG nor cytotoxicity of unsensitized and allosensitized sera to WT and GT-KO PBMC was significantly different to that of healthy sera.


CONCLUSIONS
More than half of the healthy humans tested had cytotoxic antibodies to GT-KO PBMC, but allosensitized patients will be at no greater risk of rejecting a pig xenograft by a humoral mechanism.
Hara
Hidetaka
H
Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
Ezzelarab
Mohamed
M
Rood
Pleunie P M
PP
Lin
Yih Jyh
YJ
Busch
Jamie
J
Ibrahim
Zuhaib
Z
Zhu
Xiaocheng
X
Ball
Suyapa
S
Ayares
David
D
Zeevi
Adriana
A
Awwad
Michel
M
Cooper
David K C
DK
D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D004187:Disaccharides / Q000235:genetics / Q000276:immunology; D006084:Graft Rejection; D006801:Humans; D007106:Immune Sera; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D013552:Swine / Q000235:genetics / Q000276:immunology*; D014181:Transplantation Immunology
D004187:Disaccharides; D007106:Immune Sera; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007519:Isoantigens; C055075:galactosyl-(1-3)galactose