- A simple blood test that relies on genomic sequencing can detect when a newly transplanted lung is being rejected by a patient, even when no outward signs of rejection are evident. The test could enable physicians to intervene faster and prevent or slow down chronic rejection, which is severe, irreversible, and often deadly.
The researchers, whose work was funded by the National Heart, Lung, and Blood Institute (NHLBI), also believe that this test could be useful for detecting rejection in other types of organ transplants.
Moreover, the test presents an opportunity to advance personalized medicine for lung transplant patients, as providers will be able to tailor treatments for those at highest risk for rejection.
The research team noted that lung transplant recipients have the shortest survival rates among patients who get organ transplantation of any kind, with only about half living past five years. Lung transplant patients experience high rates of chronic rejection, which occurs when the body’s immune system attacks the transplanted organ.
Existing tools for detecting rejection either require the removal of small amounts of lung tissue or are not sensitive enough to determine the severity of the rejection. The new genomic sequencing tool seems to overcome these challenges.
The experimental test, called the donor-derived cell-free DNA test, begins by obtaining a few blood droplets from the arm of a transplant recipient. A set of machines sorts the DNA fragments in the blood sample and determines which fragments are from the recipient or the donor, as well as how many of each type are present. Higher amounts of donor DNA indicate a higher risk of transplant rejection.
Researchers enrolled and monitored 106 lung transplant patients in the study. The team then tested blood samples that were collected in the first three months after transplantation.
The results showed that those with higher levels of donor-derived DNA within the first three months of transplantation were six times more likely to develop transplant organ failure or die during the study follow-up than those with lower levels of donor-derived DNA.
Notably, researchers found that more than half of high-risk subjects showed no outward symptoms of clinical complications during the follow-up period.
“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,” said Hannah Valantine, MD, co-leader of the study and lead investigator of the Laboratory of Organ Transplant Genomics in the Cardiovascular Branch at NHLBI.
“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.”
This work builds on previous studies conducted by the research team. In 2010, Valantine and her colleagues developed the first blood test to diagnose organ rejection. The following year, Valantine and her group showed that a cell-free DNA test could be useful in monitoring early signs of rejection.
However, these earlier studies only identified signs of acute transplant rejection, which can be easily reversed.
This new tool shows that if there are high levels of donor DNA present after the first three months of transplantation, then patients are experiencing chronic rejection. If validated, this blood test could become a routine tool used to monitor transplant patients at the very early stages of chronic rejection, and could improve precision medicine for transplant recipients.
“This test solves a long-standing problem in lung transplants: detection of hidden signs of rejection,” said Valantine. “We’re very excited about its potential to save lives, especially in the wake of a critical shortage of donor organs.”