Abstract

Cell-Free DNA: Potential Pan-Organ Marker for Organ Transplantation

John Sninsky, Chief Scientific Officer, CareDx Inc

Patients who have undergone organ transplants require frequent monitoring to evaluate the organ’s graft status and to modulate a complex regimen of immunosuppressive medications to address short and long term clinical needs. Sub-optimal dosing and the threat of allograft rejection must be balanced with excessive dosing and increased risks of infections and cancer. A significant unmet medical need exists for clinical diagnostic tools to permit surveillance management of transplant patients and improve the long-term outcomes of immunosuppressive therapy. Cell-free DNA (cfDNA) has been described as a biomarker for prenatal testing, cancer, and organ transplantation, each of which presents different clinical and technological challenges. cfDNA circulating in the plasma of transplant patients represents a mixture of residual nucleosomal-protected genomic regions released from dying cells of allograft (“transgenome”) and recipient cfDNA. The genomes of the organ donor and allograft recipient are distinguishable by next generation sequencing. Longitudinal samples from heart and kidney transplant patients showed significantly higher donor-derived cfDNA levels prior to biopsy-confirmed rejection which were reduced following adjustments to immunosuppressive therapy. The cfDNA compartment also harbors information about specific infectious diseases and somatic mutations associated with cancer development.  The role of Big Data in tracking organ transplantation outcomes will be discussed.