Universal noninvasive detection of solid organ transplant rejection

TM Snyder, KK Khush, HA Valantine… - Proceedings of the …, 2011 - National Acad Sciences
TM Snyder, KK Khush, HA Valantine, SR Quake
Proceedings of the National Academy of Sciences, 2011National Acad Sciences
It is challenging to monitor the health of transplanted organs, particularly with respect to
rejection by the host immune system. Because transplanted organs have genomes that are
distinct from the recipient's genome, we used high throughput shotgun sequencing to
develop a universal noninvasive approach to monitoring organ health. We analyzed cell-
free DNA circulating in the blood of heart transplant recipients and observed significantly
increased levels of cell-free DNA from the donor genome at times when an endomyocardial …
It is challenging to monitor the health of transplanted organs, particularly with respect to rejection by the host immune system. Because transplanted organs have genomes that are distinct from the recipient's genome, we used high throughput shotgun sequencing to develop a universal noninvasive approach to monitoring organ health. We analyzed cell-free DNA circulating in the blood of heart transplant recipients and observed significantly increased levels of cell-free DNA from the donor genome at times when an endomyocardial biopsy independently established the presence of acute cellular rejection in these heart transplant recipients. Our results demonstrate that cell-free DNA can be used to detect an organ-specific signature that correlates with rejection, and this measurement can be made on any combination of donor and recipient. This noninvasive test holds promise for replacing the endomyocardial biopsy in heart transplant recipients and may be applicable to other solid organ transplants.
National Acad Sciences