Is there an organ more precious than a donated heart? Heart transplant recipients would likely say no. But, in order to keep their new heart healthy, they have to identify any signs of rejection as early as possible. Unfortunately (and ironically), the gold standard procedure to detect rejection - repeated heart biopsies - involves snipping away and analyzing tiny bits of tissue from the very organ they waited so long to receive. The procedure is also uncomfortable, and can cause complications.
Now, Stanford bioengineer Stephen Quake, PhD, and his colleagues have found that a simple blood test that detects donor DNA in the bloodstream of the recipient can detect signs of rejection far earlier than biopsy. Their results were published today in Science Translational Medicine.
From our release:
The study of 65 patients (21 children and 44 adults) extends and confirms the results of a small pilot study completed in 2011 by the Stanford researchers. Whereas the earlier study used stored blood samples and medical histories from seven people, the new study followed patients in real time before and after transplant. The researchers directly compared the results of simultaneously collected biopsies and blood samples, and tracked how the values changed during the rejection process.
The blood test takes advantage of the fact that dying heart cells release genetic material into the recipient's blood. Any increase beyond a normal baseline level indicates a possible attack by the immune system on the donated organ. As described in our release:
In the pilot study of 2011, the researchers first used the presence of the Y chromosome to track the donor DNA when a woman received a heart from a male donor. Then they hit upon using differences in SNPs instead; this method doesn’t require a gender mismatch between donor and recipient. They found that, in transplant recipients not experiencing rejection, the donor DNA accounted for less than 1 percent of all cell-free DNA in the recipient’s blood. During rejection episodes, however, the percentage of donor DNA increased to about 3 or 4 percent.
In the new study, the researchers monitored 565 samples from the 65 patients to assess the assay under real-time clinical conditions. They 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 test will still need to be optimized for regular clinical use. However, cardiologist Kiran Khush, MD, a co-senior author of the study, explained what the advance could mean to heart transplant recipients:
This test has the potential to revolutionize the care of our patients... It may also allow us to conduct several diagnostic tests simultaneously. For example, we could also look for microbial sequences in the blood sample to rule out infection or other complications sometimes experienced by transplant recipients. It could allow us to determine whether shortness of breath experienced by a patient is due to an infection or the start of a rejection episode. It could be a one-stop shop for multiple potential problems.
Full disclosure: Stanford has applied for a patent relating to the test described in this study. Quake is a consultant for and holds equity in CareDX Inc., a molecular diagnostics company that has licensed a patent from Stanford related to a method used in the study and is developing it for clinical use.
Previously: 'Genome transplant' concept helps Stanford scientists predict organ rejection, Stanford study in transplant patients could lead to better treatment and New techniques to diagnose disease in a fetus
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