Adding Insult on Injury: Immunogenic Role for Donor-derived Cell-free DNA?

Donor-derived cell-free DNA (dd-cfDNA) in the blood circulation is an early marker of injury in solid organ transplantation. Here, we review recent evidence that indicates that dd-cfDNA may itself be a trigger of inflammation, thereby adding insult on injury. Early unresolving molecular allograft injury measured via changes in dd-cfDNA may be an early warning sign and may therefore enable stratification of patients who are at risk of subsequent allograft injury. Considering dd-cfDNA as a continuous and clinically significant biomarker opens up the potential for new management strategies, therapeutics, and ways to quantify interventions by considering the immunological potential of dd-cfDNA.