Donor-Derived Cell-Free DNA for Acute Rejection Monitoring in Heart and Lung Transplantation

Abstract

Purpose of review: Acute allograft rejection is a common cause of morbidity and mortality in heart and lung transplantation. Unfortunately, the current monitoring gold standard-biopsy plus histopathology-has several limitations. Plasma donor-derived cell-free DNA (dd-cfDNA) has emerged as a potentially valuable biomarker for rejection that addresses some of the limitations of biopsy. This review covers the current state of the evidence and future directions for the use of dd-cfDNA in the monitoring of acute rejection.

Recent findings: The results of several observational cohort studies demonstrate that levels of dd-cfDNA increase in the setting of acute cellular rejection and antibody-mediated rejection in both heart and lung transplant recipients. dd-cfDNA demonstrates acceptable performance characteristics, but low specificity for the detection of underlying injury from rejection or infection. In particular, the high negative predictive value of the test in both heart and lung transplant patients provides the potential for its use as a screening tool for the monitoring of allograft health rather than tissue biopsy alone.

Summary: Existing evidence shows that dd-cfDNA is a safe, convenient, and reliable method of acute rejection monitoring in heart and lung transplant recipients. Further studies are required to validate threshold values for clinical use and determine its role in the diagnosis of alternative forms of allograft injury.

Keywords: Acute rejection; Heart transplant; Lung transplant; Rejection monitoring.

Fig. 1

An illustration of the various approaches to identify donor versus recipient genetic material and an approach to quantitate or semi-quantitate levels of donor-derived cell-free DNA. cfDNA, cell-free DNA; dd-cfDNA, donor-derived cell-free DNA; NGS, next-generation sequencing; PCR, polymerase chain reaction; SNP, single nucleotide polymorphism