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

Research output: Contribution to journalArticlepeer-review

75 Citations (Scopus)

Abstract

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.

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

All Science Journal Classification (ASJC) codes

  • Immunology
  • Transplantation

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