title: Donor-specific HLA alloantibodies: Impact on cardiac allograft vasculopathy, rejection, and survival after pediatric heart transplantation.
abstract: BACKGROUND
  There is increasing evidence that donor-specific anti-HLA antibodies (DSA) are associated with poor outcomes after cardiac transplantation in adults, but data are limited in children. The objective of this study was to examine the development and consequences of de novo DSA in pediatric recipients of heart transplants.
  
  
  METHODS
  We analyzed 105 pediatric patients who received heart transplants at our center from January 2002 to December 2012. All patients had negative T-cell and B-cell post-transplant crossmatches. Patients underwent HLA antibody screening at 1, 2, 3, 6, and 12 months post-transplant and annually thereafter unless there was suspicion for rejection. HLA class I and II antibodies were identified using Luminex assay. Coronary angiography was performed at 1 year and annually thereafter. Acute cellular rejection, antibody-mediated rejection, and treated clinical rejections were included together as rejection events.
  
  
  RESULTS
  Of 105 patients, 45 (43%) developed de novo DSA. DSA-positive patients had significantly higher rates of coronary artery vasculopathy (CAV) compared with DSA-negative patients (36% vs 13%). CAV-free survival at 1 year and 5 years post-transplant for DSA-negative patients was 90% and 25%, respectively, compared with 70% and 0%, respectively, for DSA-positive patients (p < 0.01). DSA-positive patients had 2.5 times more rejection events per year than DSA-negative patients. The 5-year graft survival rate was 72.4% for DSA-negative patients and 21% for DSA-positive patients (p < 0.001).
  
  
  CONCLUSIONS
  De novo DSA has a strong negative impact on CAV, rejection, and graft survival in pediatric recipients of heart transplants.
authors.affiliation: Division of Pediatric Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Andrew
authors.initials: A
authors.lastname: Tran
authors.affiliation: Division of Pediatric Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: David
authors.initials: D
authors.lastname: Fixler
authors.affiliation: Department of Research, Children's Medical Center, Dallas, Texas.
authors.forename: Rong
authors.initials: R
authors.lastname: Huang
authors.affiliation: Division of Solid Organ Transplant, Children's Medical Center, Dallas, Texas.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Meza
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Chantale
authors.initials: C
authors.lastname: Lacelle
authors.affiliation: Division of Pediatric Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: bdas99@hotmail.com.
authors.forename: Bibhuti B
authors.initials: BB
authors.lastname: Das
mesh_terms: D000293:Adolescent; D064591:Allografts; D001402:B-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003324:Coronary Artery Disease / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D016027:Heart Transplantation / Q000401:mortality; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D007518:Isoantibodies / Q000276:immunology*; D008297:Male; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D013781:Texas / Q000453:epidemiology; D013997:Time Factors; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies
keywords: cardiac allograft vasculopathy; donor-specific anti-HLA antibodies; heart transplantation; pediatrics; rejections; survival