Journal
KIDNEY INTERNATIONAL
Volume 78, Issue 2, Pages 152-159Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/ki.2010.75
Keywords
alloantibodies; antibody-mediated rejection; complement regulation; kidney allograft; nonhuman primate
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Funding
- 'Agence de Biomedecine' (France)
- European Commission, Xenome [L5HB-CT-2006037377]
- 'Academie de Medecine' (France)
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Acute antibody-mediated rejection is an unsolved issue in transplantation, especially in the context of pretransplant immunization. The deleterious effect of preformed cytotoxic anti-HLA antibodies through complement activation is well proven, but very little is known concerning complement blockade to prevent/cure this rejection. Here, we used a baboon model of preimmunization to explore the prevention of acute antibody-mediated rejection by an early inhibition of the classical complement pathway using human recombinant C1-inhibitor. Baboons were immunized against peripheral blood mononuclear cells from allogeneic donors and, once a specific and stable immunization had been established, they received a kidney from the same donor. Rejection occurred at day 2 posttransplant in untreated presensitized recipients, with characteristic histological lesions and complement deposition. As recombinant human C1-inhibitor blocks in vitro cytotoxicity induced by donor-specific antibodies, other alloimmunized baboons received the drug thrice daily intravenously during the first 5 days after transplant. Rejection was prevented during this treatment but occurred after discontinuation of treatment. We show here that early blockade of complement activation by recombinant human C1-inhibitor can prevent acute antibody-mediated rejection in presensitized recipients. This treatment could also be useful in other forms of acute antibody-mediated rejection caused by induced antibodies. Kidney International (2010) 78, 152-159; doi:10.1038/ki.2010.75; published online 24 March 2010
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