title: Can C4d immunostaining on endomyocardial biopsies be considered a prognostic biomarker in heart transplant recipients?
abstract: BACKGROUND
  The aim of this study was to assess the significance of positive C4d capillary immunostaining of endomyocardial biopsies and its correlation to clinical outcome in adult heart transplant recipients.
  
  
  METHODS
  Nine hundred eighty-five endomyocardial biopsies from 107 heart transplant recipients were evaluated. Immunostaining for detection of intragraft C4d capillary deposition was performed on paraffin-embedded tissue using anti-human C4d polyclonal antibody.
  
  
  RESULTS
  Positive staining of C4d was present in 36 patients (34%) and antibody-mediated rejection in eight patients (7%). The patients were subdivided into four groups on the basis of their C4d, circulating antidonor antibodies (donor-specific antibodies [DSAs]), and graft function: group 1=C4d positive, DSA negative, and no graft dysfunction; group 2=C4d positive, DSA positive, and no graft dysfunction; group 3=C4d positive, DSA positive, and signs of graft dysfunction, and group 0 (control)=all negative. An higher mortality risk was found in C4d-positive patients, when compared with negative ones (unadjusted hazard ratios: group 1: 18, group 2: 61, and group 3: 32-fold risk; P<0.0001).
  
  
  CONCLUSIONS
  Antibody-mediated rejection is a complex and ongoing phenomenon with different phenotypic features. C4d positive predicts worse prognosis. C4d positive [corrected] and DSA can be used as early mortality predictors in patients without signs of graft dysfunction.
authors.affiliation: Department of Medical-Diagnostic Sciences and Special Therapies, University of Padua, Padua, Italy.
authors.forename: Marny
authors.initials: M
authors.lastname: Fedrigo
authors.forename: Antonio
authors.initials: A
authors.lastname: Gambino
authors.forename: Francesco
authors.initials: F
authors.lastname: Tona
authors.forename: Gianluca
authors.initials: G
authors.lastname: Torregrossa
authors.forename: Francesca
authors.initials: F
authors.lastname: Poli
authors.forename: Elena
authors.initials: E
authors.lastname: Benazzi
authors.forename: Annachiara
authors.initials: A
authors.lastname: Frigo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Feltrin
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Toscano
authors.forename: Alida P
authors.initials: AP
authors.lastname: Caforio
authors.forename: Sabino
authors.initials: S
authors.lastname: Iliceto
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Valente
authors.forename: Gaetano
authors.initials: G
authors.lastname: Thiene
authors.forename: Gino
authors.initials: G
authors.lastname: Gerosa
authors.forename: Annalisa
authors.initials: A
authors.lastname: Angelini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001706:Biopsy; D001787:Blood Group Incompatibility / Q000473:pathology; D002196:Capillaries / Q000473:pathology; D015935:Complement C4b / Q000032:analysis*; D004487:Edema / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D016027:Heart Transplantation / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D010446:Peptide Fragments / Q000032:analysis*; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors
chemical_list: D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d