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A new test could provide a noninvasive way of monitoring heart transplant patients for organ rejection. The test, which relies on DNA sequencing to detect fragments of the donor’s DNA in the recipient’s blood, still needs to be validated in clinical trials. But physicians hope it will ultimately offer an easy way to detect the signs of organ rejection in all types of transplant patients, perhaps earlier than other approaches.

Organ rejection is still a common problem after a heart transplant—only 50 percent of patients are alive 10 years after the procedure—and transplant recipients must undergo constant monitoring for signs of organ rejection. For people with donor hearts, this typically means an invasive cardiac biopsy weekly for the first few months, then two to three times a year after that. The procedure is uncomfortable, costly, and somewhat risky.

Biopsies detect rejection by analyzing a small piece of tissue from the donor heart for signs that the patient’s immune system is attacking the organ. But in response to an immune attack, some of the cells in the transplanted organ die, releasing DNA into the bloodstream. The new test, published today in the Proceedings of the National Academy of Sciences, detects this DNA in a sample of the patient’s blood.

In the new study, researchers first compared donor and recipient DNA, searching for single letter differences that would distinguish DNA fragments from the two sources. They then designed a sequencing-based test that could detect a genetic profile unique to the donor. Analyzing blood samples collected from 39 transplant patients over several months, they found that rising levels of donor DNA correlated with the biopsy results. “It’s a very sensitive marker,” says Hannah Valantine, a cardiologist at Stanford and one of the researchers on the study. “The ratio of donor DNA remains stable in absence of rejection. But when there is rejection, we see a rise in donor DNA.”

Valantine says she got the idea after reading a paper published by Stanford engineer Stephen Quake in 2008 that described detection of fetal DNA in maternal blood. Quake’s team then did proof-of-concept tests in female patients with male donor hearts to confirm that it was possible to find this DNA.

“The test holds a lot of promise,” says Elaine Reed, director of Transplant and Immunogenetics Testing at the University of California, Los Angeles. Reed was not involved in the study. Because the results are specific to organ rejection, the test might be applicable to other organs as well, she says. For example, liver and kidney transplant patients are monitored using a blood test for an enzyme called creatinine. But rising levels of that enzyme can be linked to different kinds of damage, not just organ rejection, and it indicates that extensive damage has already occurred.

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Credit: Hannah Valantine

Tagged: Biomedicine, DNA, sequencing, heart, transplant, organ transplants

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