title: Pathology of C4d-negative antibody-mediated rejection in renal allografts.
abstract: OBJECTIVE
  To summarize current evidence supporting the existence of C4d-negative antibody-mediated rejection (AMR) in renal allografts, its potential to cause chronic graft injury, and whether histopathologic features of C4d-negative AMR differ from those of C4d-positive AMR.
  
  
  RESULTS
  Recently published molecular, clinicopathologic, and ultrastructural studies provide strong evidence that microvascular injury in the presence of donor-specific alloantibodies (DSA) has the potential to cause interstitial fibrosis/tubular atrophy, transplant glomerulopathy, and graft loss, whether or not peritubular capillary (PTC) C4d is present. Although C4d-positive AMR may represent a more severe form of AMR, recent studies have found that in patients with DSA, microvascular injury (glomerulitis, peritubular capillaritis) is more strongly associated with graft loss than C4d deposition. Our data suggest that C4d-positive and C4d-negative AMR show similar degrees of glomerulitis and peritubular capillaritis, similar frequencies of concurrent cell-mediated rejection, and that both may occur early or late posttransplantation.
  
  
  CONCLUSIONS
  In renal allografts, microvascular injury in the presence of DSA but with negative C4d staining in PTC nonetheless is indicative of humorally mediated graft injury that has the potential to cause tubular atrophy/interstitial fibrosis, transplant glomerulopathy, and graft loss. Prompt treatment for AMR may prevent or at least delay subsequent development of transplant glomerulopathy.
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California 91403, USA. mark.haas@cshs.org
authors.forename: Mark
authors.initials: M
authors.lastname: Haas
mesh_terms: D015935:Complement C4b / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology*; D006801:Humans; D056724:Immunity, Humoral; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology*; D010446:Peptide Fragments / Q000276:immunology*; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000473:pathology
chemical_list: D007518:Isoantibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d