Immunologic risk stratification of pediatric heart transplant patients by combining HLA-EMMA and PIRCHE-II
Human leukocyte antigen (HLA) molecular mismatch is a powerful biomarker of rejection. Few studies have explored its use in assessing rejection risk in heart transplant recipients. We tested the hypothesis that a combination of HLA Epitope Mismatch Algorithm (HLA-EMMA) and Predicted Indirectly Recog...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1110292/full |
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| author | M. Ellison M. Mangiola M. Marrari C. Bentlejewski J. Sadowski D. Zern Cynthia Silvia Maria Kramer S. Heidt M. Niemann Q. Xu A. I. Dipchand W. T. Mahle J. W. Rossano C. E. Canter T. P. Singh W. A. Zuckerman D. T. Hsu B. Feingold S. A. Webber A. Zeevi |
| author_facet | M. Ellison M. Mangiola M. Marrari C. Bentlejewski J. Sadowski D. Zern Cynthia Silvia Maria Kramer S. Heidt M. Niemann Q. Xu A. I. Dipchand W. T. Mahle J. W. Rossano C. E. Canter T. P. Singh W. A. Zuckerman D. T. Hsu B. Feingold S. A. Webber A. Zeevi |
| author_sort | M. Ellison |
| collection | DOAJ |
| description | Human leukocyte antigen (HLA) molecular mismatch is a powerful biomarker of rejection. Few studies have explored its use in assessing rejection risk in heart transplant recipients. We tested the hypothesis that a combination of HLA Epitope Mismatch Algorithm (HLA-EMMA) and Predicted Indirectly Recognizable HLA Epitopes (PIRCHE-II) algorithms can improve risk stratification of pediatric heart transplant recipients. Class I and II HLA genotyping were performed by next-generation sequencing on 274 recipient/donor pairs enrolled in the Clinical Trials in Organ Transplantation in Children (CTOTC). Using high-resolution genotypes, we performed HLA molecular mismatch analysis with HLA-EMMA and PIRCHE-II, and correlated these findings with clinical outcomes. Patients without pre-formed donor specific antibody (DSA) (n=100) were used for correlations with post-transplant DSA and antibody mediated rejection (ABMR). Risk cut-offs were determined for DSA and ABMR using both algorithms. HLA-EMMA cut-offs alone predict the risk of DSA and ABMR; however, if used in combination with PIRCHE-II, the population could be further stratified into low-, intermediate-, and high-risk groups. The combination of HLA-EMMA and PIRCHE-II enables more granular immunological risk stratification. Intermediate-risk cases, like low-risk cases, are at a lower risk of DSA and ABMR. This new way of risk evaluation may facilitate individualized immunosuppression and surveillance. |
| first_indexed | 2024-04-10T00:44:13Z |
| format | Article |
| id | doaj.art-a937fe3bacc44d3ea483202828cf08f6 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T00:44:13Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a937fe3bacc44d3ea483202828cf08f62023-03-14T04:30:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-03-011410.3389/fimmu.2023.11102921110292Immunologic risk stratification of pediatric heart transplant patients by combining HLA-EMMA and PIRCHE-IIM. Ellison0M. Mangiola1M. Marrari2C. Bentlejewski3J. Sadowski4D. Zern5Cynthia Silvia Maria Kramer6S. Heidt7M. Niemann8Q. Xu9A. I. Dipchand10W. T. Mahle11J. W. Rossano12C. E. Canter13T. P. Singh14W. A. Zuckerman15D. T. Hsu16B. Feingold17S. A. Webber18A. Zeevi19University of Pittsburgh Medical Center, Histocompatibility Laboratory, Pittsburgh, PA, United StatesTransplant Institute, NYU Langone Health, New York University, New York, NY, United StatesDepartment of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesUniversity of Pittsburgh Medical Center, Histocompatibility Laboratory, Pittsburgh, PA, United StatesUniversity of Pittsburgh Medical Center, Histocompatibility Laboratory, Pittsburgh, PA, United StatesDepartment of Immunology, Leiden University Medical Center (LUMC), Leiden, NetherlandsDepartment of Immunology, Leiden University Medical Center (LUMC), Leiden, NetherlandsResearch and Development, PIRCHE AG, Berlin, GermanyDepartment of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesLabatt Heart Centre, Hospital for Sick Children, University of Toronto, Toronto, ON, CanadaChildren’s Healthcare of Atlanta, Emory University, Atlanta, GA, United StatesDivision of Cardiology, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDivision of Cardiology, Department of Pediatrics, School of Medicine, University of Washington, Seattle, WA, United States0Department of Cardiology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States1Columbia University, Irving Medical Center, New York, NY, United States2Division of Pediatric Cardiology, Children’s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York, NY, United States3Department of Pediatrics, Children’s Hospital of Pittsburgh, Pittsburgh, PA, United States4Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United StatesDepartment of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesHuman leukocyte antigen (HLA) molecular mismatch is a powerful biomarker of rejection. Few studies have explored its use in assessing rejection risk in heart transplant recipients. We tested the hypothesis that a combination of HLA Epitope Mismatch Algorithm (HLA-EMMA) and Predicted Indirectly Recognizable HLA Epitopes (PIRCHE-II) algorithms can improve risk stratification of pediatric heart transplant recipients. Class I and II HLA genotyping were performed by next-generation sequencing on 274 recipient/donor pairs enrolled in the Clinical Trials in Organ Transplantation in Children (CTOTC). Using high-resolution genotypes, we performed HLA molecular mismatch analysis with HLA-EMMA and PIRCHE-II, and correlated these findings with clinical outcomes. Patients without pre-formed donor specific antibody (DSA) (n=100) were used for correlations with post-transplant DSA and antibody mediated rejection (ABMR). Risk cut-offs were determined for DSA and ABMR using both algorithms. HLA-EMMA cut-offs alone predict the risk of DSA and ABMR; however, if used in combination with PIRCHE-II, the population could be further stratified into low-, intermediate-, and high-risk groups. The combination of HLA-EMMA and PIRCHE-II enables more granular immunological risk stratification. Intermediate-risk cases, like low-risk cases, are at a lower risk of DSA and ABMR. This new way of risk evaluation may facilitate individualized immunosuppression and surveillance.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1110292/fullPIRCHE-IIHLA-EMMAdonor specific antibodyantibody mediated rejection (ABMR)pediatric heart transplantation |
| spellingShingle | M. Ellison M. Mangiola M. Marrari C. Bentlejewski J. Sadowski D. Zern Cynthia Silvia Maria Kramer S. Heidt M. Niemann Q. Xu A. I. Dipchand W. T. Mahle J. W. Rossano C. E. Canter T. P. Singh W. A. Zuckerman D. T. Hsu B. Feingold S. A. Webber A. Zeevi Immunologic risk stratification of pediatric heart transplant patients by combining HLA-EMMA and PIRCHE-II Frontiers in Immunology PIRCHE-II HLA-EMMA donor specific antibody antibody mediated rejection (ABMR) pediatric heart transplantation |
| title | Immunologic risk stratification of pediatric heart transplant patients by combining HLA-EMMA and PIRCHE-II |
| title_full | Immunologic risk stratification of pediatric heart transplant patients by combining HLA-EMMA and PIRCHE-II |
| title_fullStr | Immunologic risk stratification of pediatric heart transplant patients by combining HLA-EMMA and PIRCHE-II |
| title_full_unstemmed | Immunologic risk stratification of pediatric heart transplant patients by combining HLA-EMMA and PIRCHE-II |
| title_short | Immunologic risk stratification of pediatric heart transplant patients by combining HLA-EMMA and PIRCHE-II |
| title_sort | immunologic risk stratification of pediatric heart transplant patients by combining hla emma and pirche ii |
| topic | PIRCHE-II HLA-EMMA donor specific antibody antibody mediated rejection (ABMR) pediatric heart transplantation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1110292/full |
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