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Additional studies are needed to confirm the results and demonstrate that patients benefit from the test; the PNAS study was based on archived tissue samples from previous biopsies. But the team now has funding from the National Institutes of Health to run the test in a set of patients about to undergo both heart and lung transplants. “Lungs may be tricky, because they can be damaged by both rejection and infection,” says Valantine. “It will be interesting to see if we can identify both.”

She also hopes the test will be able to detect rejection earlier than biopsies, which could have major benefits for patients. Treatment for organ rejection includes high doses of steroids and other drugs to suppress the immune system, leaving patients at risk for infection. “Maybe we can avoid high-dose immune suppression with early recognition and early treatment,” says Valantine. In analyzing blood samples from the first day after transplant through rejection and treatment, “we were not only able to detect a rise in donor DNA at the time of rejection, but we saw it rise before actually seeing signs of rejection on the biopsy,” she says.

Some heart transplant patients have already benefited from another type of genetic test (called Allomap) that measures expression levels in the blood of 11 genes related to the recipient’s immune response. According to a large study published in the New England Journal of Medicine, the test is highly accurate in predicting patients who are healthy and could safely forgo biopsies. But the meaning of a positive result—or highly active immune system—is less clear. These people might be rejecting the organ or have some other immune issue, and a cardiac biopsy is required to determine which. “I think there could be tremendous value of using both tests,” says Valantine. “We might be able to fully predict who is unlikely to reject and who is likely.”

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Credit: Hannah Valantine

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

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