Allosensitized humans are at no greater risk of humoral rejection of GT-KO pig organs than other humans

Hidetaka Hara; Mohamed Ezzelarab; Pleunie P M Rood; Yih Jyh Lin; Jamie Busch; Zuhaib Ibrahim; Xiaocheng Zhu; Suyapa Ball; David Ayares; Adriana Zeevi; Michel Awwad; David K C Cooper

doi:10.1111/j.1399-3089.2006.00319.x

Allosensitized humans are at no greater risk of humoral rejection of GT-KO pig organs than other humans

Hidetaka Hara, Mohamed Ezzelarab, Pleunie P M Rood, Yih Jyh Lin, Jamie Busch, Zuhaib Ibrahim, Xiaocheng Zhu, Suyapa Ball, David Ayares, Adriana Zeevi, Michel Awwad, David K C Cooper^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

97 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	357-365
Number of pages	9
Journal	Xenotransplantation
Volume	13
Issue number	4
DOIs	https://doi.org/10.1111/j.1399-3089.2006.00319.x
Publication status	Published - Jul 2006
Externally published	Yes

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10.1111/j.1399-3089.2006.00319.x

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@article{4730e7c3fd9a49459a51879ed22aff3f,

title = "Allosensitized humans are at no greater risk of humoral rejection of GT-KO pig organs than other humans",

abstract = "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.",

author = "Hidetaka Hara and Mohamed Ezzelarab and Rood, {Pleunie P M} and Lin, {Yih Jyh} and Jamie Busch and Zuhaib Ibrahim and Xiaocheng Zhu and Suyapa Ball and David Ayares and Adriana Zeevi and Michel Awwad and Cooper, {David K C}",

year = "2006",

month = jul,

doi = "10.1111/j.1399-3089.2006.00319.x",

language = "English",

volume = "13",

pages = "357--365",

journal = "Xenotransplantation",

issn = "0908-665X",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "4",

}

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 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.

AB - 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.

U2 - 10.1111/j.1399-3089.2006.00319.x

DO - 10.1111/j.1399-3089.2006.00319.x

M3 - Article

C2 - 16768729

SN - 0908-665X

VL - 13

SP - 357

EP - 365

JO - Xenotransplantation

JF - Xenotransplantation

IS - 4

ER -

Allosensitized humans are at no greater risk of humoral rejection of GT-KO pig organs than other humans

Abstract

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