Molecular-level HLA mismatch is associated with rejection and worsened graft survival in heart transplant recipients - a retrospective study.

allograft rejection antibody-verified HLA eplets cardiac allograft vasculopathy graft survival heart transplantation precision medicine

Journal

Transplant international : official journal of the European Society for Organ Transplantation
ISSN: 1432-2277
Titre abrégé: Transpl Int
Pays: Switzerland
ID NLM: 8908516

Informations de publication

Date de publication:
09 2020
Historique:
received: 04 02 2020
revised: 10 03 2020
accepted: 15 05 2020
pubmed: 23 5 2020
medline: 25 6 2021
entrez: 23 5 2020
Statut: ppublish

Résumé

The aim was to evaluate the association of molecular-level human leukocyte antigen (HLA) mismatching with post-transplant graft survival, rejection, and cardiac allograft vasculopathy (CAV). We retrospectively analyzed all primary cardiac transplant recipients between 01/1984-06/2016. 1167 patients fulfilled inclusion criteria and had HLA typing information available. In 312 donor-recipient pairs, typing at serological split antigen level was available. We used the Epitope MisMatch Algorithm to calculate the number of amino acid differences in antibody-verified HLA eplets (amino acid mismatch load (AAMM)) between donor and recipient. Patients with a higher HLA-DR AAMM load had inferior 1-year graft survival (hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.01-1.28). The HLA-AB AAMM load showed no impact on graft survival. In the subgroup with available split-level information, we observed an inferior graft survival for a higher HLA-DR AAMM load 3 months after transplantation (HR, 1.22; 95% CI, 1.04-1.44) and a higher risk for rejection for an increasing HLA-AB (HR, 1.70; 95% CI, 1.29-2.24) and HLA-DR (HR, 1.32; 95% CI, 1.09-1.61) AAMM load. No impact on the development of CAV was found. Molecular-level HLA mismatch analysis could serve as a tool for risk stratification after heart transplantation and might take us one step further into precision medicine.

Identifiants

pubmed: 32441827
doi: 10.1111/tri.13657
pmc: PMC7540475
doi:

Substances chimiques

HLA Antigens 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1078-1088

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2020 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.

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Auteurs

Emilio Osorio-Jaramillo (E)

Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.

Geert W Haasnoot (GW)

Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.

Alexandra Kaider (A)

Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria.

Anne-Kristin Schaefer (AK)

Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.

Thomas Haberl (T)

Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.

Johannes Goekler (J)

Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.

Philipp Angleitner (P)

Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.

Roxana Moayedifar (R)

Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.

Andreas Zuckermann (A)

Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.

Gottfried F Fischer (GF)

Department for Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria.

Guenther Laufer (G)

Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.

Frans H J Claas (FHJ)

Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Antwerp, Belgium.

Arezu Z Aliabadi-Zuckermann (AZ)

Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.

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