Donor-specific HLA alloantibodies: Impact on cardiac allograft vasculopathy, rejection, and survival after pediatric heart transplantation

Andrew Tran, David E Fixler, Rong Huang, Tiffany Meza, Chantale Lacelle, Bibhuti B Das

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43 Citations (Scopus)

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.

Original languageEnglish (US)
JournalJournal of Heart and Lung Transplantation
DOIs
StateAccepted/In press - 2015

Fingerprint

Isoantibodies
Heart Transplantation
Allografts
Anti-Idiotypic Antibodies
Tissue Donors
Pediatrics
Survival
Coronary Vessels
Graft Survival
Transplants
Antibodies
Coronary Angiography
B-Lymphocytes
Survival Rate

Keywords

  • Cardiac allograft vasculopathy
  • Donor-specific anti-HLA antibodies
  • Heart transplantation
  • Pediatrics
  • Rejections
  • Survival

ASJC Scopus subject areas

  • Transplantation
  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine
  • Surgery

Cite this

@article{88f8a8ff34a74cbe9e7afb31cf5aed28,
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.",
keywords = "Cardiac allograft vasculopathy, Donor-specific anti-HLA antibodies, Heart transplantation, Pediatrics, Rejections, Survival",
author = "Andrew Tran and Fixler, {David E} and Rong Huang and Tiffany Meza and Chantale Lacelle and Das, {Bibhuti B}",
year = "2015",
doi = "10.1016/j.healun.2015.08.008",
language = "English (US)",
journal = "Journal of Heart and Lung Transplantation",
issn = "1053-2498",
publisher = "Elsevier USA",

}

TY - JOUR

T1 - Donor-specific HLA alloantibodies

T2 - Impact on cardiac allograft vasculopathy, rejection, and survival after pediatric heart transplantation

AU - Tran, Andrew

AU - Fixler, David E

AU - Huang, Rong

AU - Meza, Tiffany

AU - Lacelle, Chantale

AU - Das, Bibhuti B

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - Cardiac allograft vasculopathy

KW - Donor-specific anti-HLA antibodies

KW - Heart transplantation

KW - Pediatrics

KW - Rejections

KW - Survival

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U2 - 10.1016/j.healun.2015.08.008

DO - 10.1016/j.healun.2015.08.008

M3 - Article

C2 - 26422083

AN - SCOPUS:84954078258

JO - Journal of Heart and Lung Transplantation

JF - Journal of Heart and Lung Transplantation

SN - 1053-2498

ER -