Myriad Applications of Circulating Cell-Free DNA in Precision Organ Transplant Monitoring

Abstract

Solid organ transplantation remains the preferred treatment for many end-stage organ diseases, but complications due to acute rejection and infection occur frequently and undermine its long-term benefits. Monitoring of the health of the allograft is therefore a critically important component of post-transplant therapy. Here, we review several emerging applications of circulating cell-free DNA (cfDNA) in the post-transplant monitoring of rejection, infection, and immunosuppression. We further discuss the cellular origins and salient biophysical properties of cfDNA. A property of cfDNA that has been prominent since its discovery in the late 1940s is its ability to yield surprises. We review recent insights into the epigenetic features of cfDNA that yet again provide novel opportunities for transplant monitoring.

Keywords: cell-free DNA; diagnosis; infection; patient monitoring; rejection.

Figure 1.

Cell-free DNA provides an information-rich window into human physiology with expanding applications in solid-organ transplant monitoring. Diagram of the procedure to collect, sequence, and identify donor-specific cell-free DNA (top panel; modified with permission from Reference 9). Unbiased sequencing can also be applied to observe and monitor shifts in the virome following transplantation (bottom panel; modified with permission from Reference 18).

Figure 2.

Donor-specific cell-free DNA (cfdDNA) as a measure of therapeutic response. Donor DNA levels after diagnosis and treatment of severe heart transplant rejection (International Society for Heart and Lung Transplantation grade 3R, the most severe rejection grade) (data for six patients, at rejection [red circles] and post-rejection [black circles]). Black line is fit of exponential decay model. Data from Reference .