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.