Allosensitization Does Not Increase the Risk of Xenoreactivity to ??1,3-Galactosyltransferase Gene-Knockout Miniature Swine in Patients on Transplantation Waiting Lists

Harvard University, Cambridge, Massachusetts, United States
Transplantation (Impact Factor: 3.83). 09/2006; 82(3):314-9. DOI: 10.1097/
Source: PubMed


The recent availability of alpha1,3-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.
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.
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.
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.

Download full-text


Available from: Frank Dor
  • Source
    • "Kidneys are one of the most frequently transplanted human organs, with approximately 10,000 kidney transplants being performed annually in the United States [1]. Regarding absolute numbers of kidney transplantations, Brazil ranks second among all countries, after the United States and ranks ninth per million inhabitants [2]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Kidneys are one of the most frequently transplanted human organs. Immunosuppressive agents may prevent or reverse most acute rejection episodes; however, the graft may still succumb to chronic rejection. The immunological response involved in the chronic rejection process depends on both innate and adaptive immune response. T lymphocytes have a pivotal role in chronic rejection in adaptive immune response. Meanwhile, we aim to present a general overview on the state-of-the-art knowledge of the strategies used for manipulating the lymphocyte activation mechanisms involved in allografts, with emphasis on T-lymphocyte costimulatory and coinhibitory molecules of the B7-CD28 superfamily. A deeper understanding of the structure and function of these molecules improves both the knowledge of the immune system itself and their potential action as rejection inducers or tolerance promoters. In this context, the central role played by CD28 family, especially the relationship between CD28 and CTLA-4, becomes an interesting target for the development of immune-based therapies aiming to increase the survival rate of allografts and to decrease autoimmune phenomena. Good results obtained by the recent development of abatacept and belatacept with potential clinical use aroused better expectations concerning the outcome of transplanted patients.
    Full-text · Article · Jun 2012 · Journal of Transplantation
  • [Show abstract] [Hide abstract]
    ABSTRACT: Work on delay tolerant networking has grown out of work on an interplanetary Internet and aims to provide a type of network stack which is specifically designed for use in networks with inherently long transit times - often also involving highly constrained network nodes. We present an update on progress with this technology and describe how it might be used to construct a flexible network to support both one type of Earth-based sensor network as well as future space applications.
    No preview · Conference Paper · Dec 2003
  • [Show abstract] [Hide abstract]
    ABSTRACT: Baertschiger RM, Buhler LH. Xenotransplantation literature update July–August, 2006.Xenotransplantation 2006; 13: 571–575. © Blackwell Munksgaard, 2006
    No preview · Article · Dec 2006 · Xenotransplantation
Show more