Transcriptomics in transplantation: More than just biomarkers of allograft rejection.

Disease surveillance in coronary artery disease and cancer has moved away from repetitive invasive procedures to monitor patient health and response to therapeutics. In cardiac transplantation, many centers continue to rely heavily on endomyocardial biopsies for monitoring graft function and detecting allograft rejection. The limitations of such an approach have been recognized by the community for many years, including poor agreement between pathologists in grading rejection, sampling error, variability in use of immunologic staining to detect antibody-mediated rejection (AMR), and inability to detect allograft injury in the absence of histologic findings. To address these limitations there has been an explosion of research in the field of non-invasive biomarkers to assess allograft health and diagnose both acute cellular rejection (ACR) and AMR: gene-expression profiling, donor-derived cell-free DNA, soluble cardiac protein biomarkers (e.g. troponin, natriuretic peptides), microRNAs, and exosomal proteins amongst others. Many of these biomarkers have diagnostic performance that approaches excellent with an area under the receiver operating characteristics curve (AUROC) of close to 0.90. Yet, clinical adoption has been variable as centers continue to rely on an imperfect gold standard.