title: Endothelial C4d deposition is associated with inferior kidney allograft outcome independently of cellular rejection.
abstract: BACKGROUND
  Capillary deposition of complement split product C4d has been suggested to be a valuable marker for humoral rejection. In this retrospective study we evaluated the clinical impact of C4d deposition in renal allografts with special emphasis on associations between C4d staining patterns and histological features of acute rejection.
  
  
  METHODS
  One hundred and two allograft biopsies obtained from 61 kidney transplants (1-532 days after transplantation; median 14 days) were examined by immunohistochemistry on routine paraffin sections using a novel anti-C4d polyclonal antibody (C4dpAb).
  
  
  RESULTS
  Fourty-two of 102 biopsies showed endothelial C4d deposits in peritubular capillaries (PTC). Histopathological analysis revealed a significantly lower frequency of positive C4d staining in biopsies with rather than in those without acute cellular rejection defined by the Banff grading schema (P<0.01). For clinical evaluation, patients were classified according to C4d staining in allografts (C4d(PTC) positive in at least one biopsy, n=31 vs C4d(PTC) negative in all biopsies, n=30). C4d(PTC) positive patients had significantly higher serum creatinine levels than C4d negative patients. Even in the absence of morphological evidence for rejection, differences in serum creatinine levels between C4d(PTC) positive and negative recipients were significant (6 months: 2.01+/-0.75 vs 1.41+/-0.27 mg/dl; 12 months: 1.95+/-0.60 vs 1.36+/- 0.34 mg/dl; 18 months: 1.98+/-0.50 vs 1.47+/-0.31 mg/dl; P<0.05). All patients with rejection resistant to conventional therapy (n=4) were in the C4d(PTC) positive subgroup. All recipients with panel reactive antibodies (PRA) >50% (n=8) were C4d(PTC) positive.
  
  
  CONCLUSIONS
  Our data indicate that endothelial C4d deposition is associated with inferior graft outcome. We provide evidence that this immunohistochemical finding and its clinical impact are not associated with morphological signs of cellular rejection.
authors.affiliation: Institute of Clinical Pathology, University of Vienna, Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Regele
authors.forename: M
authors.initials: M
authors.lastname: Exner
authors.forename: B
authors.initials: B
authors.lastname: Watschinger
authors.forename: C
authors.initials: C
authors.lastname: Wenter
authors.forename: M
authors.initials: M
authors.lastname: Wahrmann
authors.forename: C
authors.initials: C
authors.lastname: Osterreicher
authors.forename: M D
authors.initials: MD
authors.lastname: Säemann
authors.forename: N
authors.initials: N
authors.lastname: Mersich
authors.forename: W H
authors.initials: WH
authors.lastname: Hörl
authors.forename: G J
authors.initials: GJ
authors.lastname: Zlabinger
authors.forename: G A
authors.initials: GA
authors.lastname: Böhmig
mesh_terms: D001706:Biopsy; D003181:Complement C4 / Q000378:metabolism*; D015935:Complement C4b; D004730:Endothelium, Vascular / Q000276:immunology* / Q000473:pathology; D006084:Graft Rejection; D006801:Humans; D007150:Immunohistochemistry; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism*; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D003181:Complement C4; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d