Simple blood test may detect heart transplant rejection

US researchers said Wednesday they have developed a simple blood test that can detect heart- transplant rejection weeks or months earlier than previously possible.

The test relies on the detection of increasing amounts of the donor's DNA in the blood of the recipient, Stanford University researchers reported in the US journal Science Translational Medicine.

The findings could potentially reduce the number of biopsies that transplant patients undergo, eventually replacing the risky procedure that involves removing heart muscle tissue for analysis, they said.

"This test appears to be safer, cheaper and more accurate than a heart biopsy, which is the current gold standard to detect and monitor heart-transplant rejection," senior author Stephen Quake, professor of bioengineering and of applied physics, said in a statement. "We believe it's likely to be very useful in the clinic. "

Transplant recipients with signs of rejection can be placed on anti-rejection medications to mitigate the immune system's attack. Sometimes, however, the rejection episode is too strong and a second transplant is required.

Currently, heart-transplant recipients undergo dozens of heart biopsies in the months and years after their transplant. The biopsies are uncomfortable and may cause complications such as heart rhythm abnormalities or valve damage. It's also expensive and time-consuming, and delivers results that can be subjective or can vary according to the sampling location within the heart.

In the new study, the researchers developed a technique called cell-free DNA test for detecting heart transplant rejection that works by measuring small differences in the DNA sequences of both the transplant donor and recipient.

In a study of 65 patients, including 21 children and 44 adults, the researchers found they were able to accurately detect the two main types of rejection, antibody-mediated rejection and acute cellular rejection, in 24 patients who suffered moderate to severe rejection episodes, one of whom required a second transplant.

They were also able to detect signs of rejection up to five months before the biopsies indicated anything troubling.

The cell-free DNA test is different from another blood test, AlloMap, used to detect rejection. The commercially available AlloMap uses a blood sample to analyze the expression of immune- system genes involved in rejection. The researchers said that the cell-free DNA test outperformed AlloMap by a substantial margin.

"We've found that this cell-free DNA assay is a very accurate way to diagnose acute rejection, sometimes weeks to months before a biopsy picks up any signs," said co-senior author Kiran Khush, assistant professor of medicine at Stanford. "This earlier detection may prevent irreversible damage to the transplanted organ."

The researchers said they are optimistic that biopsies will eventually be commercially used although much remains to be done. They are also hopeful it can be generalized to detect the rejection of organs other than the heart, and to diagnose other problems such as infections that plague organ transplant recipients.