title: Correlation of circulating donor-specific anti-HLA antibodies and presence of C4d in endomyocardial biopsy with heart allograft outcomes: a single-center, retrospective study.
abstract: BACKGROUND
  Donor-specific antibodies (DSA) are associated with increased cardiac graft loss and cardiac vasculopathy (CAV). Detection of antibody-mediated rejection (AMR) relies on graft dysfunction, C4d immunofluorescence (IF) and DSA.
  
  
  METHODS
  We retrospectively studied the relationship of DSA, endomyocardial biopsy (EMB) and C4d IF to cardiac transplant outcomes. DSA were evaluated against HLA class I and II specificities, both pre- and post-transplant, using microbead-based assays.
  
  
  RESULTS
  Of 626 cardiac transplant patients, 109 with concurrent EMBs and C4d IF and DSA measurement were included in this study. In patients with and without DSA, CAV occurred in 31% and 13% and acute cellular rejection (ACR) in 100% and 84%, respectively. One hundred ten of 170 EMBs procured during episodes of graft dysfunction had concurrent DSA. In these patients, C4d IF correlated better with DSA to class I or both class I and II and less so in patients with DSA to class II. Graft failure (GF) rates of 40%, 29% and 58% with average times to GF of 33, 77 and 48 months were seen in patients with DSA to class I, II or both, respectively.
  
  
  CONCLUSIONS
  Patients with DSA to class I or to both class I and II showed a correlation with C4d IF and had higher GF rates compared to patients with DSA to only class II or no DSA; patients with DSA to class II remained at risk for CAV. Episodes of ACR and CAV, but not AMR, appeared to be more frequently associated with graft dysfunction in patients with circulating DSA.
authors.affiliation: Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: Renee
authors.initials: R
authors.lastname: Frank
authors.forename: Maria R
authors.initials: MR
authors.lastname: Molina
authors.forename: Joyce W
authors.initials: JW
authors.lastname: Wald
authors.forename: Lee R
authors.initials: LR
authors.lastname: Goldberg
authors.forename: Malek
authors.initials: M
authors.lastname: Kamoun
authors.forename: Priti
authors.initials: P
authors.lastname: Lal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood*; D015935:Complement C4b / Q000032:analysis; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry / Q000276:immunology* / Q000473:pathology*; D010446:Peptide Fragments / Q000032:analysis; D012189:Retrospective Studies; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d