Anatomic pathologists may be reading fewer biopsy reports for patients with organ transplants in the future. That’s thanks to a new technology that may be more sensitive to and capable of detecting organ rejection earlier than traditional needle biopsies.
When clinicians can detect organ transplant rejection earlier, patients survive longer. Unfortunately, extensive organ damage may have already occurred by the time rejection is detected through a traditional needle biopsy. This led a group of researchers at Emory University School of Medicine to search for a better method for detecting organ rejection in patients with transplants.
The Emory researchers describe the method and technology they devised in a paper published in Nature Biomedical Engineering, titled, “Non-Invasive Early Detection of Acute Transplant Rejection Via Nanosensors of Granzyme B Activity.” The new technology could make it easier for clinicians to detect when a patient’s body is rejecting a transplanted organ at an earlier time than traditional methods.
This technology also provides a running measure of processes, so clinicians have more powerful tools for deciding on the most appropriate dosage of immunosuppressant drugs.
“Right now, most tests are aimed at organ dysfunction, and sometimes they don’t signal there is a problem until organ function is below 50 percent,” Andrew Adams, MD, PhD Co-Principal Investigator and an Associate Professor of Surgery at Emory University School of Medicine, in a Georgia Institute of Technology news release.
How the Technology Works
The method that Adams and his colleagues tested involves the detection of granzyme B, a serine protease often found in the granules of natural killer cells (NK cells) and cytotoxic T cells. “Before any organ damage can happen, T cells have to produce granzyme B, which is why this is an early detection method,” said Gabe Kwong, PhD, Assistant Professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, in the news release.
The new technology is made up of sensor nanoparticles in the shape of a ball with iron oxide in the middle. Amino acids stick out of the ball like bristles. Each amino acid has a fluorescent molecule attached to the tip.
The nanoparticles are injected into the patient. Their size prevents them from gathering in the patient’s tissue or from being flushed out through the kidneys. They are designed to accumulate in the tissue of the transplanted organ.
If the T cells in the transplanted organ begin to produce granzyme B, the amino acids break away from the nanoparticles, releasing the fluorescent molecules attached to their tips. Those molecules are small enough to be processed through the kidneys and can be detected in the patient’s urine.
Pathologists Play Crucial Role on Transplant Teams
Anatomical pathologists (histopathologists in the UK) are key members of transplant teams for many reasons, including their ability to assess biopsies. The current method for detecting organ transplant rejection involves needle biopsies. It is considered the gold standard.
However, according to a paper published in the International Journal of Organ Transplantation Medicine: “Although imaging studies and laboratory findings are important and helpful in monitoring of the transplanted liver, in many circumstances they are not sensitive enough. For conditions such as rejection of the transplant, liver histology remains the gold-standard test for the diagnosis of allograft dysfunction. Therefore, histopathologic assessments of allograft liver biopsies have an important role in managing patients who have undergone liver transplantation.”
There are two main problems with needle biopsies. The first, as mentioned above, is that they don’t always catch the rejection soon enough. The second is that the needle may cause damage to the transplanted organ.
And, according to Kwong, even though biopsies are the gold standard, the results represent one moment in time. “The biopsy is not predictive. It’s a static snapshot. It’s like looking at a photo of people in mid-jump. You don’t know if they’re on their way up or on their way down. With a biopsy, you don’t know whether rejection is progressing or regressing.”
Future Directions of Emory’s Research
The research conducted by Adams and Kwong, et al, is in its early stages, and the new technology they created won’t be ready to be used on patients for some time. Nevertheless, there’s reason to be excited.
Nanoparticles are not nearly as invasive as a needle biopsy. Thus, risk of infection or damaging the transplanted organ is much lower. And Emory’s technology would allow for much earlier detection, as well as giving clinicians a better way to adjust the dose of immunosuppressant drugs the patient takes.
“Adjusting the dose is very difficult but very important because heavy immunosuppression increases occurrence of infections and patients who receive it also get cancer more often,” said Kwong. The new technology provides a method of measuring biological activity rates, which would give clinicians a clearer picture of what’s happening.
The Emory team’s plan is to enhance the new sensors to detect at least one other major cause of transplant rejection—antibodies. When a patient’s body rejects a transplanted organ, it produces antibodies to neutralize what it sees as a foreign entity.
“Antibodies kill their target cells through similar types of enzymes. In the future, we envision a single sensor to detect both types of rejection,” said Kwong.
Adams adds, “This method could be adapted to tease out multiple problems like rejection, infection, or injury to the transplanted organ. The treatments for all of those are different, so we could select the proper treatment or combination of treatments and also use the test to measure how effective treatment is.”
This line of research at Emory University demonstrates how expanding knowledge in a variety of fields can be combined in new ways. As this happens, medical laboratories not only get new biomarkers that can be clinically useful without the need for invasive procedures like needle biopsies, but these same biomarkers can guide the selection of more effective therapies.