title: Incidence and Outcome of C4d Staining With Tubulointerstitial Inflammation in Blood Group-incompatible Kidney Transplantation.
abstract: BACKGROUND
  The last Banff 2013 report recognizes acute/active antibody-mediated rejection (ABMR) and C4d staining without evidence of rejection. The goal of our study was to analyze the incidence of C4d deposition after ABO-incompatible transplantation and assess outcomes in patients with ABMR, C4d staining without evidence of rejection (all acute Banff scores = 0), and C4d staining with tubulointerstitial inflammation (i > 0 with or without tubulitis).
  
  
  METHODS
  Three-months 'For cause' or protocol biopsies in 50 ABO-incompatible patients were rescored and were correlated with clinical outcomes and antibody titres.
  
  
  RESULTS
  Active/acute ABMR was found in 23 patients (46%), C4d staining without evidence of rejection in 7 patients (14%), C4d staining with tubulointerstitial inflammation in 6 patients (12%), tubulointerstitial inflammation in 6 patients (12%), and no evidence of rejection in 8 patients (16%). Patients with active/acute ABMR had a 3-month estimated glomerular filtration rate (median,: 43 mL/min) lower than patients with no evidence of rejection (median, 61 mL/min; P = 0.01). However, after 3 months, a progressively declining estimated glomerular filtration rate was observed more frequently in patients with C4d staining and tubulointerstitial inflammation when compared to patients with no evidence of rejection (100% vs 25%, P = 0.03). Finally, independently of C4d status, interstitial inflammation occurred more frequently in patients with a pretransplant ABO antibody titre higher than 16 and/or posttransplant ABO antibody increase.
  
  
  CONCLUSIONS
  Whereas isolated C4d deposition and isolated interstitial inflammation appear to be benign lesions, C4d deposition in association with interstitial inflammation is the biopsy finding most strongly associated with the development of chronic graft dysfunction.
authors.affiliation: 1 Department of Transplantation, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. 2 Department of Histopathology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. 3 Medical Research Council Centre for Transplantation, King's College, London, United Kingdom. 4 Clinical Transplant Laboratory, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom. 5 Great Ormond Street Hospital for Children, NHS Foundation Trust, London, United Kingdom.
authors.forename: Lionel
authors.initials: L
authors.lastname: Couzi
authors.forename: Ranmith
authors.initials: R
authors.lastname: Perera
authors.forename: Miriam
authors.initials: M
authors.lastname: Manook
authors.forename: A Nicholas R
authors.initials: AN
authors.lastname: Barnett
authors.forename: Olivia
authors.initials: O
authors.lastname: Shaw
authors.forename: Nicos
authors.initials: N
authors.lastname: Kessaris
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Marks
authors.forename: Anthony
authors.initials: A
authors.lastname: Dorling
authors.forename: Nizam
authors.initials: N
authors.lastname: Mamode
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology*; D000208:Acute Disease; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D001787:Blood Group Incompatibility / Q000150:complications* / Q000175:diagnosis / Q000276:immunology; D015935:Complement C4b / Q000032:analysis*; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology* / Q000503:physiopathology; D006648:Histocompatibility; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D007668:Kidney / Q000276:immunology* / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008131:London / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology* / Q000503:physiopathology; D010446:Peptide Fragments / Q000032:analysis*; D010641:Phenotype; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000017:ABO Blood-Group System; D015415:Biomarkers; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d