Blood Test for Donor DNA Improves Detection of Rejection

A sophisticated molecular method has been used to detect the DNA of the donor in the blood of heart transplant patients, which will aid in early recognition of rejection.

An increase in the amount of the donor's DNA in the recipient's blood is one of the earliest detectable signs of organ rejection and can be evaluated using a microfluidic digital polymerase chain reaction (PCR).

Scientists at Stanford University School of Medicine (Stanford, CA, USA) developed advanced genome-sequencing technology to measure levels of donor DNA released when cells in the transplanted heart are damaged as occurs early in the rejection process. A study of 39 samples from women with male hearts showed that the prevalence of the Y chromosome in the recipient's blood increased significantly, from a norm of about 0.5% of the total, up to 8%, during episodes of rejection. They also used an existing blood test that relies on the expression profile of 20 genes in a patient's blood sample to determine whether the body has launched an attack on the donated organ. The original Allomap blood test is produced by XDX Diagnostics, (Brisbane, CA, USA). The two methods in tandem will allow the noninvasive monitoring of the health of many transplanted organs, including hearts, lungs and kidneys.

The analysis of the cell-free DNA circulating in the blood of heart transplant recipients showed 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 the heart transplant recipients. Rejection episodes corresponded to levels of donor DNA approaching 3% to 4%, so when the patients were successfully treated with immunosuppressants, the amount of the donor DNA in the blood decreased to less than 1% of total free DNA. The high throughput shotgun sequencing method that was developed leads to a universal noninvasive approach to monitoring organ health.

The 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. Stephen Quake, PhD, who developed the sequencing technology, said, "This approach, which we call genome transplant dynamics, or GTD, solves a long-standing problem in cardiac transplantation. It is so difficult to find and implant a donor heart, and then doctors have to remove pieces of it every few months to test for rejection." The study was published online on March 28, 2011, in the Proceedings of the National Academy of Sciences of the Unites States of America (PNAS).

Related Links:
Stanford University School of Medicine
XDX Diagnostics