Recent evidence indicates that plasma donor-derived cell-free DNA (dd-cfDNA) is a sensitive biomarker for the detection of underlying allograft injury, including rejection and infection. In this review, we will cover the latest evidence revolving around dd-cfDNA in lung transplantation and its role in both advancing mechanistic insight into disease states in lung transplant recipients as well as its potential clinical utility.

Plasma dd-cfDNA increases in the setting of allograft injury, including in primary graft dysfunction, acute cellular rejection, antibody-mediated rejection and infection. Dd-cfDNA has demonstrated good performance characteristics for the detection of various allograft injury states, most notably with a high negative-predictive value for detection of acute rejection. Elevated levels of dd-cfDNA in the early posttransplant period, reflecting molecular evidence of lung allograft injury, are associated with increased risk of chronic lung allograft dysfunction and death.

As a quantitative, molecular biomarker of lung allograft injury, dd-cfDNA holds great promise in clinical and research settings for advancing methods of posttransplant surveillance monitoring, diagnosis of allograft injury states, monitoring adequacy of immunosuppression, risk stratification and unlocking pathophysiological mechanisms of various disease.