Blood test may detect early signs of lung-transplant rejection

After receiving a lung transplant, patients face the likely chance that their body’s immune system will reject the transplanted organ. Rejection can happen at any time due to a variety of factors such as a lung infection or an injury to the lungs during transplant surgery. The most deadly type of rejection is chronic lung allograft rejection (CLAD), which develops slowly and often without obvious symptoms.

Now, researchers have developed a simple blood test that detects tissue graft injury within the first three months after lung transplant surgery. After further validation, this non-invasive test could identify patients with a high risk of CLAD or death due to graft failure, allowing doctors to intervene early and possibly prevent chronic rejection.

“This test solves a long-standing problem in lung transplants: detection of hidden signs of rejection,” said Hannah Valantine, MD, a co-leader of the study and a senior investigator at the National Heart, Lung, and Blood Institute, in a recent news release. “We’re very excited about its potential to save lives, especially in the wake of a critical shortage of donor organs.”

Valantine is also a Stanford professor of medicine and Kiran Khush, MD, associate professor of medicine, is a co-senior author.

The new test identifies and quantifies DNA fragments circulating freely in a patient’s bloodstream. Since the lung donor and recipients have different genomes, the test can spot fragments from both people. If there are a lot more donor DNA fragments than recipient fragments, this indicates that the organ is injured.

As recently reported in EBioMedicine, the researchers regularly monitored blood samples from 106 lung transplant patients during the first three months after surgery at several institutions, including Stanford. After dividing the patients into three groups based on the level of donor-derived DNA fragments in their blood, the team found that patients with higher levels were six times more likely to subsequently develop transplant organ failure or die than those with lower levels. And many of these high-risk patients didn’t have symptoms.

“We showed for the first time that donor-derived DNA is a predictive marker for chronic lung rejection and death, and could provide critical time-points to intervene, perhaps preventing these outcomes,” Valantine said in the release. “Once rejection is detected early via this test, doctors would then have the option to increase the dosages of anti-rejection drugs, add new agents that reduce tissue inflammation, or take other measures to prevent or slow the progression.”

The researchers expect commercial versions of the blood test to be available for clinical use soon. They are also planning future studies to evaluate the blood test for other solid organ transplants.

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