文献_2011-PNAS-Universal noninvasive detection of solid organ transplant rejection.pdf

Universal noninvasive detection of solid organ transplant rejection a,b c c,1 a,b,1 Thomas M. Snyder , Kiran K. Khush , Hannah A. Valantine , and Stephen R. Quake aThe Howard Hughes Medical Institute and bDepartments of Applied Physics and Bioengineering, Stanford University, Stanford, CA 94305; and cDivision of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305 Edited* by Leonard A. Herzenberg, Stanford University, Stanford, CA, and approved February 24, 2011 (received for review September 15, 2010) It is challenging to monitor the health of transplanted organs, par- donor-specific chromosome Y has been detected in recipient urine ticularly with respect to rejection by the host immune system. Be- and plasma (16–19). To date, most measurements of cell-free DNA cause transplanted organs have genomes that are distinct from the in organ transplantation have been limited to the special case of recipient’s genome, we used high throughput shotgun sequencing women who receive male organs, which has prevented the wide- to develop a universal noninvasive approach to monitoring organ spread use of cell-free DNA as a diagnostic tool, because female health. We analyzed cell-free DNA circulating in the blood of heart recipients of male donor organs represent less than a quarter of all transplant procedures. HLA markers can be quantified to identify transplant recipients and observed significantly increased levels of donor-derived DNA in pancreas–kidney transplant recipients (20), cell-free DNA from the donor genome at times when an endomyocar-