title: Utility of C4d immunostaining in the first year after pediatric and young adult heart transplantation.
abstract: BACKGROUND
  C4d assessment of endomyocardial biopsies (EMBs) after heart transplantation (HTx) has been widely adopted to aid in the diagnosis of antibody-mediated rejection (AMR), yet it remains unclear whether or not to assess all patients routinely and with what frequency/duration. In this study we sought to evaluate the utility of routine C4d immunostaining in the first year after pediatric and young adult HTx.
  
  
  METHODS
  We reviewed pre-transplant alloantibody and clinical data, including serial EMB reports, on all 51 patients who received HTx at our center since we instituted routine C4d staining of all first-year EMBs. C4d was considered positive if diffuse capillary staining (≥ 2(+)) was present. Rare/focal capillary staining or absence of staining was considered negative.
  
  
  RESULTS
  Twenty-six of 406 first-year EMBs (6%) were C4d(+) in 6 (12%) patients. Sixty-five percent of all C4d(+) EMBs occurred by 30 days post-transplant. Five of 6 patients had pre-transplant donor-specific antibody (DSA) ≥ 4,000 MFI. The sixth patient had neither pre-transplant anti-HLA antibodies nor a positive donor-specific cytotoxicity crossmatch (DSXM), but there was clinical concern for AMR. Among the entire cohort, 5 of 10 patients with pre-transplant DSA ≥ 4,000 MFI and/or a positive DSXM were C4d(+) compared with only 1 of 41 without (50% vs 2%; p = 0.001).
  
  
  CONCLUSIONS
  In the first year after HTx, C4d(+) occurred early and only in children and young adults with pre-transplant DSA or with clinical suspicion of AMR. Although our data suggest that assessment limited to the first 90 days post-transplant in patients with pre-transplant DSA ≥ 4,000 MFI may be appropriate in the absence of clinical concern for AMR, further research is needed to determine the optimum strategy for post-transplant surveillance.
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Csaba
authors.initials: C
authors.lastname: Galambos
authors.forename: Miguel
authors.initials: M
authors.lastname: Reyes-Múgica
authors.forename: Susan A
authors.initials: SA
authors.lastname: Miller
authors.forename: Adriana
authors.initials: A
authors.lastname: Zeevi
authors.forename: Steven A
authors.initials: SA
authors.lastname: Webber
authors.forename: Brian
authors.initials: B
authors.lastname: Feingold
mesh_terms: D000293:Adolescent; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D015935:Complement C4b / Q000032:analysis*; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010446:Peptide Fragments / Q000032:analysis*; D013997:Time Factors; D055815:Young Adult
chemical_list: D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d