title: C4D immunostaining in surveillance endomyocardial biopsies from well-functioning heart allografts.
abstract: OBJECTIVE
  The meaning of biopsy C4d detection in heart allografts without dysfunction or morphologic changes suggesting antibody-mediated rejection (AMR) is not clear. The aim of this study was to search for an association between C4d detection in allograft biopsies of well-functioning hearts without changes suggestive of AMR, and clinical outcomes.
  
  
  METHODS
  Endomyocardial protocol biopsies from 44 heart transplant patients with well-functioning grafts and without changes suggesting AMR were performed at 1 month and 1 year after transplantation and analyze the presence of C4d deposition using immunohistochemistry. Two-year follow-up was based on clinical parameters and echocardiographic information. Heart graft function was categorized as good vs. poor. The presence of C4d, using diverse schemes to graduate the extension of the deposition, was correlated with clinical graft outcomes.
  
  
  RESULTS
  C4d deposition was observed in the capillary walls of 33 biopsies (37.5%; n = 25 patients; 56.8%). No biopsy had diffuse (>50%) immunostaining. Six patients presented with multifocal capillary C4d immunostaining in at least 1 biopsy. Capillary positivity for C4d (if focal or multifocal) showed no statistical association with cellular rejection or graft function. Perimyocytic C4d detection was neither associated with rejection nor graft outcome.
  
  
  CONCLUSIONS
  Our work failed to demonstrate an association between C4d detection in protocol biopsies of heart grafts and clinical outcomes. The clinical utility of C4d staining in solid organ transplantation may vary by organ. Our results suggest that C4d did not have clinical utility in surveillance biopsies of well-functioning heart grafts without morphological changes suggesting AMR.
authors.affiliation: PRYT Group, Department of Pathology, Faculty of Medicine, University of Antioquia, Medellin, Colombia. lfarias@kidneypathology.com
authors.forename: L F
authors.initials: LF
authors.lastname: Arias
authors.forename: R
authors.initials: R
authors.lastname: Fernández
authors.forename: D
authors.initials: D
authors.lastname: Fernández
authors.forename: J C
authors.initials: JC
authors.lastname: Jaramillo
authors.forename: M
authors.initials: M
authors.lastname: Gil
authors.forename: J A
authors.initials: JA
authors.lastname: López García-Asenjo
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D002196:Capillaries / Q000276:immunology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015935:Complement C4b / Q000032:analysis*; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology*; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis*; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d