The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2022
Immunologic risk stratification of pediatric heart transplant patients by combining HLAMatchmaker and PIRCHE-II.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Mangiola Massimo, Ellison Mitchell A, Marrari Marilyn, Bentlejewski Carol, Sadowski John, Zern Dwayne, Niemann Matthias, Feingold Brian, Webber Steve A, Zeevi Adriana, CTOTC-09 site investigators
Аннотация
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.
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.