Donor DNA May Identify Early Heart Transplant Rejection

Scientists are reporting a new way to identify when a heart transplant recipient 1 is starting to reject the new organ. The new technique could help doctors ensure the success of more transplants.

The human immune system is programmed to reject foreign bodies. It's how we fight off infections. That's one of the biggest obstacles in organ transplant: the body sees the new organ as foreign.

So transplant recipients 2 take powerful immunosupressant drugs, but rejection 3 still happens. If discovered early enough, doctors may be able to adjust the patient's medications. If not, they may need another transplant...assuming an organ is available.

To monitor for rejection of heart transplants, doctors examine the new heart for signs of rejection every couple of months.

"The current gold standard to look for rejection is to actually physically 4 biopsy the heart, which means the doctors go in and rip a piece of it out and look at it under a microscope," says Stanford University researcher Stephen Quake, who calls the procedure "rather medieval."

"The key insight for this work was to realize that a heart transplant is really a genome transplant. When someone else's heart gets put inside your body, all the cells in that organ have that person's genome, which is different than yours. And so, if you sequence DNA 5 from the blood, you can tell which DNA is coming specifically from the heart as opposed to other organs by those small differences in the genome."

Scientists have long known that the blood contains bits of DNA, which were in cells that have since died. And if a transplanted heart is being rejected, it will have more dead cells, and shed more DNA.

"When the organ is being rejected, your immune system is attacking it and the cells become very unhealthy and start to die, and when they die they spill their genome into the blood," Quake explains. "And so you'd expect an increase in the amount of heart DNA in the blood to be a direct consequence of damage to the heart. And that's, in fact, what we showed in this paper."

For this research, Quake studied heart transplant patients, but he says he believes the same method could be used for other kinds of organ transplants, too. That would give doctors a non-invasive, early warning of organ rejection, which can be controlled in many cases by adjusting the patient's anti-rejection medications.

The Stanford University researcher describes the DNA-based method of identifying organ rejection online in the Proceedings 6 of the National Academy of Sciences.