Can C4d immunostaining on endomyocardial biopsies be considered a prognostic biomarker in heart transplant recipients?
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.
Fedrigo
Marny
M
Department of Medical-Diagnostic Sciences and Special Therapies, University of Padua, Padua, Italy.
Gambino
Antonio
A
Tona
Francesco
F
Torregrossa
Gianluca
G
Poli
Francesca
F
Benazzi
Elena
E
Frigo
Annachiara
A
Feltrin
Giuseppe
G
Toscano
Giuseppe
G
Caforio
Alida P
AP
Iliceto
Sabino
S
Valente
Marialuisa
M
Thiene
Gaetano
G
Gerosa
Gino
G
Angelini
Annalisa
A
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
D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d