NIH Research Matters
April 18, 2011
Blood DNA Test Detects Heart Transplant Rejection
A new type of test that detects “foreign” DNA in a patient’s bloodstream may provide early clues to organ rejection. The technique could offer an alternative to the expensive and invasive biopsies now used to detect transplant failure.
Organ transplantation saves the lives of thousands of Americans each year. But recipients are at risk for transplant rejection, in which the immune system attacks and damages the donated organ. Researchers have been searching for biomarkers in the blood that might serve as early signs of organ rejection and allow quick intervention, but results to date have been mixed.
For the new study, Drs. Hannah Valantine and Stephen Quake of Stanford University collaborated to develop a blood test to detect heart transplant failure. They hypothesized that blood levels of foreign DNA from the donated organ would rise during rejection, as transplanted heart cells began to die and burst open. The idea stemmed from Quake’s earlier development of a noninvasive prenatal test for birth defects. He’d shown that the free-floating pieces of fetal DNA in a pregnant woman’s bloodstream could be rapidly sequenced to detect abnormalities. The work was supported in part by an NIH Director’s Pioneer Award.
To evaluate the new technique, called genome transplant dynamics, the scientists analyzed DNA fragments found in 71 blood samples from 17 heart transplant recipients. The samples had been collected at various points after transplantation. The results were reported in the April 12, 2011, edition of the Proceedings of the National Academy of Sciences.
By comparing the proportions of DNA derived from the organ donor and recipient, the scientists determined that, when patients were healthy, donor DNA made up less than 1% of the total free-floating DNA in the blood samples. During rejection episodes, however, the proportion of donor DNA rose to 3-4%. After successful treatment with immunosuppressive drugs, the proportion of donor DNA tended to decline, in some cases returning to less than 1%.
“In every case we could see an increase in donor DNA in the patient's blood before the biopsy itself showed any sign of rejection,” Valantine says. “Heart transplant recipients undergo at least 12 tissue biopsies during the first year after their transplant and 2 or 3 each year for about 4 additional years. The idea that we might now be able to diagnose rejection earlier and noninvasively is very, very exciting.”
“For the first time, we can now use cell-free DNA for practical diagnostic questions in organ transplantation,” says Quake, adding that the approach may apply to other organs.
More evidence will be needed to see whether this approach can lead to a reliable clinical test, either alone or in conjunction with other approaches. With funding from NIH’s National Institute of Allergy and Infectious Diseases (NIAID), the scientists are now evaluating how well genome transplant dynamics can diagnose acute rejection of heart and lung transplants.
—by Vicki Contie
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