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

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.

• Publication year

  2020

• Venue

  Transplant International

• Publication date

  2020-05-22

• Fields of study

  Medicine

• Identifiers
  DOI 10.1111/tri.13657PMID 32441827PMCID 7540475
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: 23rd pediatric heart transplantation report-2020; focus on deceased donor characteristics.

  2020cited by this paper
• Towards the identification of the relative immunogenicity of individual HLA antibody epitopes.

  2019cited by this paper
• The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-sixth adult heart transplantation report - 2019; focus theme: Donor and recipient size match.

  2019cited by this paper
• A Novel Tool to Define the Immunogenicity of HLA Mismatches

  2018cited by this paper
• The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-fifth Adult Heart Transplantation Report-2018; Focus Theme: Multiorgan Transplantation.

  2018cited by this paper
• The Registry of the International Society for Heart and Lung Transplantation: Thirty-fourth Adult Heart Transplantation Report-2017; Focus Theme: Allograft ischemic time.

  2017cited by this paper
• Epitope-Based HLA Matching: A Useful Strategy With Many Shortcomings to Overcome.

  2017cited by this paper
• HLA Epitope Matching in Kidney Transplantation: An Overview for the General Nephrologist.

  2017cited by this paper
• Class II Eplet Mismatch Modulates Tacrolimus Trough Levels Required to Prevent Donor-Specific Antibody Development.

  2017cited by this paper
• HLA Matching at the Eplet Level Protects Against Chronic Lung Allograft Dysfunction

  2016cited by this paper
• HLA‐DR and ‐DQ Eplet Mismatches and Transplant Glomerulopathy: A Nested Case–Control Study

  2015cited by this paper
• The Synergistic Effect of Class II HLA Epitope‐Mismatch and Nonadherence on Acute Rejection and Graft Survival

  2015cited by this paper
• HLA molecular epitope mismatching and long-term graft loss in pediatric heart transplant recipients.

  2015cited by this paper
• Differences in Immunogenicity of HLA Antigens and the Impact of Cross-Reactivity on the Humoral Response

  2014cited by this paper
• Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations

  2014cited by this paper
• Class II HLA Epitope Matching—A Strategy to Minimize De Novo Donor‐Specific Antibody Development and Improve Outcomes

  2013cited by this paper
• The 2013 International Society for Heart and Lung Transplantation Working Formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation.

  2013cited by this paper
• 16th IHIW: A Website for Antibody‐Defined HLA Epitope Registry

  2012influential reference
• Creation of a quantitative recipient risk index for mortality prediction after cardiac transplantation (IMPACT).

  2011cited by this paper
• International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010.

  2010cited by this paper
• Registry of the International Society for Heart and Lung Transplantation: Twenty-sixth Official Adult Heart Transplant Report-2009.

  2009cited by this paper
• A structurally based approach to determine HLA compatibility at the humoral immune level.

  2006cited by this paper
• Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection.

  2005cited by this paper
• Differential immunogenicity of HLA mismatches in clinical transplantation.

  2005cited by this paper
• HLA MATCHMAKER: A MOLECULARLY BASED ALGORITHM FOR HISTOCOMPATIBILITY DETERMINATION

  2003cited by this paper
• HLAMatchmaker: a molecularly based algorithm for histocompatibility determination. I. Description of the algorithm.

  2002cited by this paper
• HLAMMATCHMAKER: a molecularly based donor selection algorithm for highly alloimmunized patients.

  2001cited by this paper
• Influence of HLA matching on thoracic transplant outcomes. An analysis from the UNOS/ISHLT Thoracic Registry.

  1996cited by this paper
• The influence of HLA compatibility on graft survival after heart transplantation. The Collaborative Transplant Study.

  1994cited by this paper
• HLA compatibility and cardiac transplant recipient survival.

  1987cited by this paper

• Combined molecular mismatch scores for immunologic risk stratification in pediatric heart transplantation.

  2025cites this paper
• Belatacept-based immunosuppression in heart transplant recipients: A single center experience

  2025cites this paper
• Role of HLA matching and donor specific antibody development in long-term survival, acute rejection and cardiac allograft vasculopathy.

  2024cites this paper
• Cardiac Replacement Therapy: critical issues and future perspectives of Heart Transplantation and Artificial Heart.

  2024cites this paper
• Association of HLA B‐ and T‐cell molecular mismatches with HLA antibodies, rejection, and graft survival in pediatric kidney transplantation

  2024cites this paper
• DQA1 Eplet Mismatch Load As an Independent Risk Factor of CLAD After Lung Transplantation

  2023cites this paper
• Heart Transplant HLA Matching in the Modern Era.

  2023cites this paper
• HLA sensitization is associated with an increased risk of primary graft dysfunction after heart transplantation.

  2023cites this paper
• Comparison of HLA immunological risk stratification methods in lung transplantation.

  2023cites this paper
• De Novo Donor-Specific Antibodies after Heart Transplantation: A Comprehensive Guide for Clinicians

  2023cites this paper
• Challenges of CRISPR/Cas-Based Cell Therapy for Type 1 Diabetes: How Not to Engineer a “Trojan Horse”

  2023cites this paper
• Liquid Biopsy, a Potential New Detection Method in Heart Allograft Rejection.

  2023cites this paper
• Major technological advances will enhance Australian donor‐recipient matching and improve transplant outcomes

  2023cites this paper
• Primary Graft Dysfunction Is Associated With Development of Early Cardiac Allograft Vasculopathy, but Not Other Immune-mediated Complications, After Heart Transplantation

  2023cites this paper
• Immunologic risk stratification of pediatric heart transplant patients by combining HLA-EMMA and PIRCHE-II

  2023cites this paper
• Impact of assigning 2‐field HLA alleles from real‐time PCR on deceased donor assessments and conformance with high resolution alleles

  2023cites this paper
• Determining Clinical Thresholds for Donor HLA Eplet Compatibility to Predict Best Outcomes Following Lung Transplantation

  2022cites this paper
• Human leukocyte antigen epitope mismatch loads and the development of de novo donor‐specific antibodies in cardiothoracic organ transplantation

  2021cites this paper
• Epitope-Level Matching—A Review of the Novel Concept of Eplets in Transplant Histocompatibility

  2021cites this paper
• Further evidence on HLA‐DR matching in determining heart transplantation outcomes

  2020influential citation
• HLA‐EMMA, a tool for molecular‐level HLA matching after heart transplantation

  2020cites this paper
• Physicians' All-Inclusive Guide on De Novo Donor-Specific Antibodies after Heart Transplantation

  year unknowncites this paper