title: Acute cellular rejection: impact of donor-specific antibodies and C4d.
abstract: BACKGROUND
  Mixed rejection in kidney transplantation consists of histologic and/or serological evidence of both cellular and humoral components. As it is not confined to a distinct category in the Banff classification, how to best manage these patients is not clear. The aim of this study was to determine the incidence and outcome of morphological T-cell-mediated rejection (TCMR) with a humoral component, defined as the presence of either DSA or C4d, compared with the outcome of pure TCMR.
  
  
  METHODS
  We retrospectively studied 922 consecutive renal transplant recipients and analyzed patients with TCMR according to the evidence of a humoral component.
  
  
  RESULTS
  A total of 147 cases of morphological TCMR were analyzed. Of these, 92 (62.6%) had "pure" TCMR and 55 (37.4%) had "mixed" TCMR on the index biopsy. On univariant analysis, diffuse C4d (odds ratio [OR]=10.9, 95% confidence interval [CI]=1.8-66.9, P=0.01) and DSA positivity at the time of index biopsy (OR=2.8, 95% CI=1.2-6.6, P=0.02) were associated with allograft loss, whereas arteritis (OR=0.5, 95% CI=0.2-1.2, P=0.11) and glomerulitis (OR=0.9, 95% CI=0.4-2.1, P=0.8) were not. Arteritis was associated with subsequent antibody-mediated rejection (OR=4.9, 95% CI=1.1-20.8, P=0.03), and glomerulitis was associated with the development of transplant glomerulopathy (OR=10.7, 95% CI=3.1-37.1, P<0.01). On the multivariate analysis, only patients with C4d and DSA were at risk of graft failure (OR=4.9, 95% CI=2.0-12.0, P<0.01) in the medium term.
  
  
  CONCLUSIONS
  TCMR with a humoral component has a worse prognosis when compared with pure TCMR. As such, it is important to test for alloantibody in cases of morphological TCMR to optimize patient management. Such cases might benefit from more aggressive immunotherapy.
authors.affiliation: 1 Imperial College Kidney and Transplant Centre, Hammersmith Hospital, London, UK. 2 Department of histopathology, Imperial College NHS Trust, London, UK. 3 Department of Histocompatibility and Immunogenetics, Imperial College NHS Trust, London, UK. 4 Centre for Complement and Inflammation Research, Imperial College, London, UK. 5 Address correspondence to: Michelle Willicombe, Imperial College Kidney and Transplant Centre, Hammersmith Hospital, London, UK W12 0HS.
authors.forename: Michelle
authors.initials: M
authors.lastname: Willicombe
authors.forename: Candice
authors.initials: C
authors.lastname: Roufosse
authors.forename: Paul
authors.initials: P
authors.lastname: Brookes
authors.forename: Adam G
authors.initials: AG
authors.lastname: McLean
authors.forename: Jack
authors.initials: J
authors.lastname: Galliford
authors.forename: Tom
authors.initials: T
authors.lastname: Cairns
authors.forename: Terry H
authors.initials: TH
authors.lastname: Cook
authors.forename: David
authors.initials: D
authors.lastname: Taube
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology; D001167:Arteritis / Q000276:immunology; D001706:Biopsy; D002196:Capillaries / Q000276:immunology; D015935:Complement C4b / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods; D007518:Isoantibodies / Q000276:immunology; D007678:Kidney Glomerulus / Q000276:immunology; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010446:Peptide Fragments / Q000276:immunology*; D011379:Prognosis; D051437:Renal Insufficiency / Q000276:immunology* / Q000628:therapy; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000166:cytology; D013997:Time Factors; D014019:Tissue Donors
chemical_list: D000906:Antibodies; D007518:Isoantibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d