title: Association between C4d staining in renal transplant biopsies, production of donor-specific HLA antibodies, and graft outcome.
abstract: BACKGROUND
  We carried out a retrospective study of C4d staining in paraffin sections from renal transplant biopsies to determine the association between C4d staining, donor-specific antibodies (DSA), histological features, and graft outcome.
  
  
  METHODS
  We studied 92 patients who had been biopsied for graft dysfunction. Biopsies were classified using Banff 97 criteria and features suggestive of antibody-mediated rejection were noted. Paraffin sections were stained with a polyclonal antibody using an immunoperoxidase technique. The presence of DSA in concurrent sera was determined by enzyme-linked immunosorbent assay and clinical data were reviewed.
  
  
  RESULTS
  Of the 92 cases, 15% showed diffuse and 24% showed focal C4d positivity. The grafts failed in 36% of the diffuse (P<0.025), 23% of the focal, and 7% of the negative group at between one month and 15 years posttransplantation. Only patients in the group with diffuse C4d positivity had concurrent DSA (five cases, P<0.001). Of the five DSA-positive patients, three had type II acute rejection and two of these transplants subsequently failed. The remaining two had chronic allograft nephropathy with features of alloimmune injury. Only two of the nine DSA-negative/C4d-positive transplants had failed at the time of writing, in one case due to recurrent disease.
  
  
  CONCLUSIONS
  We demonstrated a significant association between diffuse C4d staining, production of DSA, and graft failure. Although the concurrent detection of DSA and C4d positivity is uncommon in our patients, these results indicate that outcome in this group is poor and they may benefit from therapies directed at the humoral response.
authors.affiliation: Transplantation Laboratory, Manchester Institute of Nephrology and Transplantation, Manchester Royal Infirmary, Manchester United Kingdom. judith.worthington@cmmc.nhs.uk
authors.forename: Judith E
authors.initials: JE
authors.lastname: Worthington
authors.forename: Anna
authors.initials: A
authors.lastname: McEwen
authors.forename: Lorna J
authors.initials: LJ
authors.lastname: McWilliam
authors.forename: Michael L
authors.initials: ML
authors.lastname: Picton
authors.forename: Susan
authors.initials: S
authors.lastname: Martin
mesh_terms: D000906:Antibodies / Q000276:immunology* / Q000378:metabolism*; D001706:Biopsy; D003181:Complement C4 / Q000378:metabolism*; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D012189:Retrospective Studies; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D003181:Complement C4