TY - JOUR
T1 - Allosensitized humans are at no greater risk of humoral rejection of GT-KO pig organs than other humans
AU - Hara, Hidetaka
AU - Ezzelarab, Mohamed
AU - Rood, Pleunie P.M.
AU - Lin, Yih Jyh
AU - Busch, Jamie
AU - Ibrahim, Zuhaib
AU - Zhu, Xiaocheng
AU - Ball, Suyapa
AU - Ayares, David
AU - Zeevi, Adriana
AU - Awwad, Michel
AU - Cooper, David K.C.
PY - 2006/7
Y1 - 2006/7
N2 - Background: The availability of pigs homozygous for α1,3- galactosyltransferase gene-knockout (GT-KO) has enabled study of the incidence and cytotoxicity of primate antibodies directed to antigens other than Galα1,3Gal (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.
AB - Background: The availability of pigs homozygous for α1,3- galactosyltransferase gene-knockout (GT-KO) has enabled study of the incidence and cytotoxicity of primate antibodies directed to antigens other than Galα1,3Gal (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.
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U2 - 10.1111/j.1399-3089.2006.00319.x
DO - 10.1111/j.1399-3089.2006.00319.x
M3 - Article
C2 - 16768729
AN - SCOPUS:33745094078
SN - 0908-665X
VL - 13
SP - 357
EP - 365
JO - Xenotransplantation
JF - Xenotransplantation
IS - 4
ER -
