PMID- 35437211
OWN - NLM
STAT- MEDLINE
DCOM- 20220629
LR  - 20221004
IS  - 1557-3117 (Electronic)
IS  - 1053-2498 (Linking)
VI  - 41
IP  - 7
DP  - 2022 Jul
TI  - Immunologic risk stratification of pediatric heart transplant patients by 
      combining HLAMatchmaker and PIRCHE-II.
PG  - 952-960
LID - S1053-2498(22)01883-6 [pii]
LID - 10.1016/j.healun.2022.03.015 [doi]
AB  - BACKGROUND: Molecular-level human leukocyte antigen (HLA) mismatch is a powerful 
      biomarker of rejection; however, few studies have explored its use in heart 
      transplant recipients, and none have attempted to use the results of separate 
      algorithms synergistically. Here we tested the hypothesis that a combination of 
      HLAMatchmaker and Predicted Indirectly Recognizable HLA Epitopes (PIRCHE-II) can 
      be used to identify more patients at low risk of rejection. METHODS: We studied 
      274 recipient/donor pairs enrolled in the Clinical Trials in Organ 
      Transplantation in Children (CTOTC) performing class I and II HLA genotyping by 
      next-generation sequencing to determine eplet mismatch (epMM) load and PIRCHE-II 
      score. Correlation with clinical outcomes was performed on 131 cases. RESULTS: Of 
      the 131 patients, 100 without pre-formed donor specific antibody (DSA) were used 
      to identify cutoffs for the Class I, HLA-DR, and HLA-DQ epMM load and PIRCHE-II 
      score for risk of developing post-transplant DSA (epMM: Class I/DR/DQ = 9/9/6; 
      PIRCHE-II: 141/116/111) and antibody-mediated rejection (ABMR) (epMM: 9/8/8; 
      PIRCHE-II: 157/80/201). Patients with above cut-off epMM load appear to be less 
      likely to develop DSA and ABMR if their PIRCHE-II score is below cut-off (high 
      epMM/high PIRCHE-II: 12.3%-20.3% DSA and 9%-13.5% ABMR vs high epMM/low 
      PIRCHE-II: 4%-10% DSA and 0%-2% ABMR). CONCLUSION: For the first time in a 
      pediatric heart transplant cohort, immunologic risk cut-offs for DSA and ABMR 
      have been established. When used together, epMM load and PIRCHE-II score allow us 
      to reclassify a portion of cases with high epMM load as having a lower risk for 
      developing DSA and ABMR.
CI  - Copyright (c) 2022 International Society for Heart and Lung Transplantation. 
      Published by Elsevier Inc. All rights reserved.
FAU - Mangiola, Massimo
AU  - Mangiola M
AD  - Transplant Institute, NYU Langone Health, New York, New York. Electronic address: 
      Massimo.Mangiola@nyulangone.org.
FAU - Ellison, Mitchell A
AU  - Ellison MA
AD  - University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania.
FAU - Marrari, Marilyn
AU  - Marrari M
AD  - Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
FAU - Bentlejewski, Carol
AU  - Bentlejewski C
AD  - Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
FAU - Sadowski, John
AU  - Sadowski J
AD  - University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania.
FAU - Zern, Dwayne
AU  - Zern D
AD  - University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania.
FAU - Niemann, Matthias
AU  - Niemann M
AD  - PIRCHE AG, Berlin, Germany.
FAU - Feingold, Brian
AU  - Feingold B
AD  - Pediatric Heart Failure and Heart Transplant Program, Children's Hospital of 
      Pittsburgh, Pittsburgh, Pennsylvania.
FAU - Webber, Steve A
AU  - Webber SA
AD  - Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, 
      Tennessee.
FAU - Zeevi, Adriana
AU  - Zeevi A
AD  - Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
CN  - CTOTC-09 site investigators
AD  - CTOTC-09 site investigators* Anne I. Dipchand, Department of Pediatrics, Hospital 
      for Sick Children, Labatt Family Heart Center, Toronto, Ontario, Canada* 
      Jaqueline M. Lamour, Department of Pediatrics, Icahn School of Medicine at Mt. 
      Sinai, New York, NY, USA* William T. Mahle, Division of Pediatric Cardiology, 
      Children's Healthcare of Atlanta, Atlanta, GA, USA* Joseph W. Rossano, Division 
      of Pediatric Cardiology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA* Janet N. Scheel, Division of Pediatric Cardiology, Washington University 
      School of Medicine, St. Louis, MO, USA* Tajinder P. Singh, Department of 
      Pediatric Cardiology, Boston Children's Hospital, Boston, MA, USA* Warren A. 
      Zuckerman, Division of Pediatric Cardiology, Columbia University Medical Center, 
      New York, NY, USA.
LA  - eng
GR  - U01 AI104336/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220330
PL  - United States
TA  - J Heart Lung Transplant
JT  - The Journal of heart and lung transplantation : the official publication of the 
      International Society for Heart Transplantation
JID - 9102703
RN  - 0 (Antibodies)
RN  - 0 (Epitopes)
RN  - 0 (HLA Antigens)
RN  - 0 (Isoantibodies)
SB  - IM
MH  - Antibodies
MH  - Child
MH  - Epitopes/*immunology
MH  - Graft Rejection
MH  - Graft Survival
MH  - HLA Antigens
MH  - *Heart Transplantation
MH  - Histocompatibility Testing/methods
MH  - Humans
MH  - Isoantibodies
MH  - *Kidney Transplantation
MH  - Risk Assessment
MH  - Tissue Donors
OTO - NOTNLM
OT  - HLAMatchmaker
OT  - PIRCHE-II
OT  - antibody mediated rejection
OT  - donor specific antibody
OT  - heart transplant
OT  - molecular mismatch
EDAT- 2022/04/20 06:00
MHDA- 2022/06/30 06:00
CRDT- 2022/04/19 05:43
PHST- 2021/08/09 00:00 [received]
PHST- 2022/03/23 00:00 [revised]
PHST- 2022/03/24 00:00 [accepted]
PHST- 2022/04/20 06:00 [pubmed]
PHST- 2022/06/30 06:00 [medline]
PHST- 2022/04/19 05:43 [entrez]
AID - S1053-2498(22)01883-6 [pii]
AID - 10.1016/j.healun.2022.03.015 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2022 Jul;41(7):952-960. doi: 
      10.1016/j.healun.2022.03.015. Epub 2022 Mar 30.