Recombinant human C1-inhibitor prevents acute antibody-mediated rejection in alloimmunized baboons
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...
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Published in | Kidney international Vol. 78; no. 2; pp. 152 - 159 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
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Basingstoke
Elsevier Inc
01.07.2010
Nature Publishing Group Elsevier Limited |
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Abstract | 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. |
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AbstractList | 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. |
Author | Poirier, Nicolas Minault, David Vistoli, Fabio Daha, Mohamed Le Bas-Bernardet, Stéphanie Hervouet, Jeremy Blancho, Gilles Tillou, Xavier Soulillou, Jean Paul Renaudin, Karine Karam, Georges |
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Copyright | 2010 International Society of Nephrology 2015 INIST-CNRS Copyright Nature Publishing Group Jul 2010 |
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Keywords | complement regulation kidney allograft nonhuman primate alloantibodies antibody-mediated rejection Graft(material) Nephrology Complement C1 Monkey Transplantation Homotransplantation Urology Isoimmunization Prevention Regulation(control) Surgery Primates Graft Recombinant protein Human Antibody Acute Nonhuman primate Baboon Rejection Vertebrata Mammalia Treatment Alloantibody Inhibitor |
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SubjectTerms | Acute Disease alloantibodies Animals Antibodies - immunology antibody-mediated rejection Biological and medical sciences Complement C1 Inhibitor Protein - therapeutic use Complement Inactivating Agents - therapeutic use complement regulation Disease Models, Animal Graft Rejection - immunology Graft Rejection - prevention & control Immunization kidney allograft Kidney Transplantation - immunology Medical sciences Nephrology. Urinary tract diseases nonhuman primate Papio Recombinant Proteins - therapeutic use |
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Title | Recombinant human C1-inhibitor prevents acute antibody-mediated rejection in alloimmunized baboons |
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