Allosensitization does not increase the risk of xenoreactivity to α1,3-galactosyltransferase gene-knockout miniature swine in patients on transplantation waiting lists

Banny S. Wong, Kazuhiko Yamada, Masayoshi Okumi, Joshua Weiner, Patricia E. O'Malley, Yau Lin Tseng, Frank J.M.F. Dor, David K.C. Cooper, Susan L. Saidman, Adam Griesemer, David H. Sachs

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58 Citations (Scopus)

Abstract

BACKGROUND. The recent availability of α1,3-galactosyltransferase knockout (GalT-KO) miniature swine has eliminated anti-Gal antibodies as the major barrier to xenotransplantation, potentially bringing this modality closer to clinical application. Highly-allosensitized patients, who have poor prospects of receiving a suitable cross-match negative human organ, might be the first patients to benefit from xenotransplantation of porcine organs. However, concerns exist regarding cross-reactivity of alloreactive anti-human leukocyte antigen (HLA) antibodies against xenogeneic swine leukocyte antigen (SLA) antigens. We have investigated this question using sera from such patients on GalT-KO target cells. METHODS. Using flow cytometry and complement-dependent cytotoxicity (CDC) assays, we have tested a panel of 88 human serum samples from patients awaiting cadaveric renal allotransplantation for reactivity against: 1) human; 2) standard miniature swine; and 3) GalT-KO peripheral blood lymphocytes (PBL) and cultured endothelial cells. RESULTS. Anti-swine IgM and IgG antibody binding, as well as CDC, were significantly attenuated on GalT-KO versus standard swine. No correlation was found between the degree of anti-human panel reactive antibodies (PRA) and xenoreactivity against either standard or GalT-KO miniature swine. Treatment of sera with dithiothreitol (DTT) showed that the majority of remaining lymphocytotoxicity against GalT-KO swine was mediated by preformed IgM antibodies. Patients with high alloreactivity but low anti-GalT-KO xenoreactivity were readily identified. CONCLUSIONS. Highly allosensitized patients awaiting renal transplants appear to be at no increased risk of xenosensitization over their non-sensitized cohorts, and could therefore be candidates for xenotransplantation using GalT-KO swine donors.

Original languageEnglish
Pages (from-to)314-319
Number of pages6
JournalTransplantation
Volume82
Issue number3
DOIs
Publication statusPublished - 2006

All Science Journal Classification (ASJC) codes

  • Transplantation

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