title: Complement modulation in solid-organ transplantation.
abstract: The complement system is a major constituent of the innate immune system. It has a critical role in defense against pathogens but dysregulation of complement activation may lead to tissue injury and modulate the adaptive immune response. In organ transplantation, local complement activation is involved in hyper-acute rejection and antibody-mediated rejection. This last decade, interest in complement activation has increased due to new insights into the pathophysiology of antibody-mediated rejection, but also since the availability of news drugs that target terminal complement activation. In this review, we discuss our current understanding of how local complement activation induces acute and chronic graft injury, and review recent advances in clinical trials that block complement activation using the anti-C5 monoclonal antibody, eculizumab. Finally, we discuss how complement-targeted therapy may be integrated into our current immunosuppressive regimen and what type of patient will benefit most from this therapy.
authors.affiliation: Nephrology Department, IFRNT, Le Kremlin-Bicêtre, France; Institut National de la Santé et de la Recherche Médicale INSERM U1014, Villejuif, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Touzot
authors.affiliation: Nephrology Department, IFRNT, Le Kremlin-Bicêtre, France.
authors.forename: Erika Nnang
authors.initials: EN
authors.lastname: Obada
authors.affiliation: Nephrology Department, IFRNT, Le Kremlin-Bicêtre, France; Institut National de la Santé et de la Recherche Médicale INSERM U1014, Villejuif, France.
authors.forename: Severine
authors.initials: S
authors.lastname: Beaudreuil
authors.affiliation: Nephrology Department, IFRNT, Le Kremlin-Bicêtre, France; Institut National de la Santé et de la Recherche Médicale INSERM U1014, Villejuif, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: François
authors.affiliation: Nephrology Department, IFRNT, Le Kremlin-Bicêtre, France; Institut National de la Santé et de la Recherche Médicale INSERM U1014, Villejuif, France. Electronic address: antoine.durrbach@bct.aphp.fr.
authors.forename: Antoine
authors.initials: A
authors.lastname: Durrbach
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D003167:Complement Activation / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D006801:Humans; D016377:Organ Transplantation; D014181:Transplantation Immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003165:Complement System Proteins; C481642:eculizumab