Can C4d immunostaining on endomyocardial biopsies be considered a prognostic biomarker in heart transplant recipients?

Transplantation. 2010 Oct 15;90(7):791-8. doi: 10.1097/TP.0b013e3181efd059.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Analysis of Variance
  • Biopsy
  • Blood Group Incompatibility / pathology
  • Capillaries / pathology
  • Complement C4b / analysis*
  • Edema / pathology
  • Endothelium, Vascular / pathology
  • Female
  • Follow-Up Studies
  • Heart Transplantation / mortality
  • Heart Transplantation / pathology*
  • Humans
  • Male
  • Middle Aged
  • Myocardium / pathology*
  • Peptide Fragments / analysis*
  • Prognosis
  • Risk Factors
  • Survival Rate
  • Time Factors


  • Peptide Fragments
  • Complement C4b
  • complement C4d