title: The role of complement in antibody-mediated rejection in kidney transplantation.
abstract: Over the past decade, several studies have suggested that the complement system has an active role in both acute and chronic allograft rejection. These studies have been facilitated by improved techniques to detect antibody-mediated organ rejection, including immunohistological staining for C4d deposition in the allograft and solid-phase assays that identify donor-specific alloantibodies (DSAs) in the serum of transplant recipients. Studies with eculizumab, a humanized monoclonal antibody directed against complement component C5, have shown that activation of the terminal complement pathway is necessary for the development of acute antibody-mediated rejection in recipients of living-donor kidney allografts who have high levels of DSAs. The extent to which complement activation drives chronic antibody-mediated injury leading to organ rejection is less clear. In chronic antibody-mediated injury, early complement activation might facilitate chemotaxis of inflammatory cells into the allograft in a process that later becomes somewhat independent of DSA levels and complement factors. In this Review, we discuss the different roles that the complement system might have in antibody-mediated allograft rejection, with specific emphasis on renal transplantation.
authors.affiliation: Department of Surgery, Division of Transplantation Surgery and von Liebig Transplant Center, 200 First Street SW, Mayo Clinic, Rochester, MN 55905, USA. stegall.mark@mayo.edu
authors.forename: Mark D
authors.initials: MD
authors.lastname: Stegall
authors.forename: Marcio F
authors.initials: MF
authors.lastname: Chedid
authors.forename: Lynn D
authors.initials: LD
authors.lastname: Cornell
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000906:Antibodies / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized; D003167:Complement Activation / Q000276:immunology / Q000502:physiology*; D003181:Complement C4 / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology*; D007684:Kidney Tubules / Q000276:immunology
chemical_list: D000906:Antibodies; D061067:Antibodies, Monoclonal, Humanized; D003181:Complement C4; C481642:eculizumab