C1-inhibitor for prophylaxis of xenograft rejection after pig to cynomolgus monkey kidney transplantation

Transplantation
J M HeckerM Winkler

Abstract

Early rejection of discordant porcine xenografts in primate recipients is initiated by the intragraft binding of either preformed (hyperacute xenograft rejection) or induced (acute vascular rejection) antiporcine recipient antibodies with subsequent complement activation via the classical pathway. We have investigated the efficacy of the supplemental administration of C1-inhibitor (C1-INH), a specific inhibitor of the classical complement activation pathway, for prophylaxis of xenograft rejection in a pig to primate kidney xenotransplantation setting. Based on the results of pharmacokinetic studies performed in two nontransplanted monkeys, supplemental C1-INH therapy was administered daily to three Cynomolgus monkeys receiving a life-supporting porcine kidney transplant together with cyclophosphamide-induction/cyclosporine A/mycophenolat-mofetil/steroid immunosuppressive therapy. In the three monkeys receiving porcine kidney xenografts and continuous C1-INH treatment none of the grafts underwent hyperacute rejection; all xenografts showed initial function. Recipient survival was 13, 15, and 5 days. No graft was lost due to acute vascular rejection. All animals died with a functioning graft (latest creatinine 96, 112, and 96 mic...Continue Reading

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Citations

Aug 14, 2003·Molecular Immunology·Tom E Mollnes, Arnt E Fiane
Aug 14, 2003·Molecular Immunology·Luigi Bergamaschini, Marco Cicardi
Dec 16, 2003·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Carsten SchröderRichard N Pierson
Feb 25, 2011·Critical Care : the Official Journal of the Critical Care Forum·Mervyn Singer, Annie M Jones
Jul 11, 2008·Expert Opinion on Biological Therapy·Diana WoutersSacha Zeerleder
Jul 31, 2012·Transplantation Proceedings·W RamackersM Winkler
Apr 21, 2009·Transplant Immunology·Richard N Pierson
Aug 5, 2008·Molecular Immunology·Alvin E DavisFengxin Lu
Jan 1, 2019·Transplant International : Official Journal of the European Society for Organ Transplantation·Wolf RamackersAndreas Tiede
May 3, 2005·Transplant International : Official Journal of the European Society for Organ Transplantation·Monica E WinklerUlrich Martin
Aug 19, 2006·Journal of Biochemistry·Chizuko KobayashiShuji Miyagawa

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