Universal noninvasive detection of solid organ transplant rejection

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2011-04, Vol.108 (15), p.6229-6234
Main Authors: Snyder, Thomas M., Khush, Kiran K., Valantine, Hannah A., Quake, Stephen R., Herzenberg, Leonard A.
Format: Article
Language:English
Subjects:
Biological Sciences
Biopsies
Blood
Blood plasma
Cells
Chromosomes, Human, Y - genetics
Deoxyribonucleic acid
DNA
DNA - blood
DNA - genetics
Gene expression
Genomics
Graft rejection
Graft Rejection - blood
Graft Rejection - diagnosis
Graft Rejection - pathology
Heart Transplantation
High-Throughput Nucleotide Sequencing - methods
Humans
Immune system
Monitoring, Physiologic - methods
Organ donation
Polymerase chain reaction
Polymorphism, Single Nucleotide
Sequencing
Sex chromosomes
Tissue Donors
Transplantation
Transplants & implants
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1013924108