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 journalArticleAcademicpeer-review

94 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 languageEnglish
Pages (from-to)357-365
Number of pages9
JournalXenotransplantation
Volume13
Issue number4
DOIs
Publication statusPublished - Jul 2006
Externally publishedYes

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