Analysis of the control of the anti-gal immune response in a non-human primate by galactose alpha1-3 galactose trisaccharide-polyethylene glycol conjugate.
Transplantation
; 73(11): 1780-7, 2002 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-12085001
BACKGROUND: The current limitation to the clinical application of xenotransplantation using pig organs is a rejection process that has been termed delayed xenograft rejection or acute vascular rejection. It is thought that acute vascular rejection may be mediated at least in part by both the continued synthesis, of preexisting, and the induction, posttransplantation, of antibodies against the carbohydrate moiety galalpha1-3gal that is present on glycoproteins and glycolipids of the pig endothelium. The synthesis of these antibodies has proven difficult to control with currently available immunosuppressive agents. METHODS: We have synthesized galalpha1-3gal conjugated polyethylene glycol polymers that can bind to anti-galalpha1-3gal antibodies and tested their activity in non-human primates. RESULTS: These conjugates when administered to non-human primates can substantially reduce the levels of preexisting and control the induction of anti-galalpha1-3gal antibodies. The level of circulating antibody-secreting cells that make anti-galalpha1-3gal antibodies is also reduced. CONCLUSION: These alpha-gal polyethylene glycol conjugates may have the potential to control the anti-gal antibody response in a pig to primate organ transplant setting and may be a useful therapeutic agent in prolonging graft survival.
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Base de dados:
MEDLINE
Assunto principal:
Transplante Heterólogo
/
Anticorpos Heterófilos
/
Transplante de Coração
/
Dissacarídeos
/
Rejeição de Enxerto
Limite:
Animals
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article