The evolution of patient-specific precision biomarkers to guide personalized heart-transplant care. Issue 1 (2nd January 2021)

• Record Type: Journal Article
• Authors: Deng, Mario C.
• Is Part Of: Expert review of precision medicine and drug development. Volume 6:Issue 1(2021)
• Page Start: 51
• Page End: 63
• Publication Date: 2021-01-02
• Subjects: Heart transplantation -- allograft rejection -- endomyocardial biopsy -- peripheral blood mononuclear cell transcriptome profiling -- cell-free DNA -- outcome prediction -- organ dysfunction -- biomarker -- precision medicine -- personalized medicine; Personalized medicine -- Periodicals; Drug development -- Periodicals; 615.19005
• DOI: 10.1080/23808993.2021.1840273
• Languages: English
• ISSNs: 2380-8993

Abstract

ABSTRACT: Introduction: In parallel to the clinical maturation of heart transplantation over the last 50 years, rejection testing has been revolutionized within the systems biology paradigm triggered by the Human Genome Project. Areas covered: We have co-developed the first FDA-cleared diagnostic and prognostic leukocyte gene expression profiling biomarker test in transplantation medicine that gained international evidence-based medicine guideline acceptance to rule out moderate/severe acute cellular cardiac allograft rejection without invasive endomyocardial biopsies. This work prompted molecular re-classification of intragraft biology, culminating in the identification of a pattern of intragraft myocyte injury, in addition to acute cellular rejection and antibody-mediated rejection. This insight stimulated research into noninvasive detection of myocardial allograft injury. The addition of a donor-organ specific myocardial injury marker based on donor-derived cell-free DNA further strengthens the noninvasive monitoring concept, combining two complementary noninvasive blood-based measures, host immune activity-related risk of acute rejection as well as cardiac allograft injury. Expert opinion: This novel complementary noninvasive heart transplant monitoring strategy based on leukocyte gene expression profiling and donor-derived cell-free DNA that incorporates longitudinal variability measures provides an exciting novel algorithm of heart transplant allograft monitoring. This algorithm's clinical utility will need to be tested in an appropriately designed randomized clinical trial.