Looking for DNA debris: blood test detects organ transplant rejection

A noninvasive genetic test can help doctors monitor the health of transplanted organs. This could diagnose rejection earlier and without surgical biopsies.
Written by Janet Fang, Contributor

A noninvasive genetic test can help doctors monitor the health of transplanted organs and diagnose rejection earlier (and without surgical biopsies).

To determine if a heart transplant is being rejected, doctors rely on risky, and sometimes unreliable, heart biopsies.

"It's so difficult to find and implant a donor heart, and then doctors have to remove pieces of it every few months to test for rejection,” says study author Stephen Quake of Stanford. It’s also slow, painful, and costly.

So a team of Stanford scientists looked for a noninvasive way in the genes.

DNA from the donor tags along with every donated organ – this is what’s known as the concurrent genome transplant. Because transplanted organs have genomes that are distinct from the recipient’s genome, the team turned to genetic sequencing.

Freely circulating DNA (that is, without cells) is released when cells in the transplanted heart are damaged. This DNA is essentially debris shed by the transplanted organ as it's progressively demolished by the recipient's immune system, New Scientist explains.

Thus, elevated levels of cell-free donor-DNA is a sure sign of cell death – and organ rejection. Their method – known as genome transplant dynamics – detects those unique genetic signatures of the circulating donor-DNA.

"There is always a baseline level of DNA from the donor floating around in the blood of the recipient," says Quake. "But when the pieces reach a certain level it gives us a very powerful predictor that a rejection event is going on."

So they measured the relative amounts of donor-DNA in the plasma of 44 blood samples taken from 7 recipients at various stages of success and failure.

  • In the blood of recipients with healthy transplanted hearts, the level of donor-DNA was below 1% of their total cell-free DNA.
  • In the blood of patients who rejected the transplanted heart, the relative level of donor-DNA hovered around 3-4%.

They verified their test in 70 transplant recipients receiving biopsies. "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,” says study author Hannah Valantine of Stanford.

That’s good because these patients undergo at least 12 biopsies during the first year post-transplant and up to 3 each year for about 4 additional years.

But unfortunately, signs of rejection are treated aggressively with large doses of immunosuppressive drugs, which have additional side effects including diabetes, hypertension, and kidney problems.

Current genetic tests hinge on detecting the male Y chromosome in the plasma of female recipients. But the pairing of women with male hearts is less than a quarter of all organ transplants.

Because the blood test is cheaper and simpler, it could save the $12 million spent annually on biopsies in the US – and it can eventually be applied to all transplants. The researchers have filed a patent.

The study was published today in the Proceedings of the National Academy of Sciences.

Image: glitterina.com via Flickr

This post was originally published on Smartplanet.com

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