New Blood Test Could Predict Organ Rejection Before Symptoms Appear

Breakthrough Test Predicts Organ Transplant Rejection with Blood Biomarkers: A Major Step in Precision Medicine

For millions of organ transplant recipients, one of the most enduring fears is whether their transplanted organ will be rejected by their immune system. While transplant success rates have significantly improved over the years, the risk of rejection persists as a constant concern. Rejection can occur at any point after surgery, often without any immediate symptoms, and once it happens, the damage can be irreversible, necessitating another transplant or causing severe health complications.

Currently, the only reliable way to diagnose organ rejection is through an invasive biopsy, a procedure that comes with its own set of risks and challenges. But a recent breakthrough offers a new hope for transplant patients: a non-invasive blood test that can predict whether an organ is being rejected—before the situation becomes dire. This revolutionary test, based on biomarkers identified across multiple types of transplanted organs, could transform how we monitor transplant health and improve patient outcomes globally.

The Problem of Organ Rejection

Organ rejection occurs when the body’s immune system recognizes the transplanted organ as foreign and mounts an immune response to destroy it. The risk of rejection can vary based on the type of organ, the immunosuppressive drugs used, and the individual patient's immune system. Rejection episodes may occur at any time—immediately after surgery, months later, or even years down the line. In some cases, rejection might be symptomless, making it difficult for doctors to detect until the organ is severely damaged.

Rejection rates also differ significantly by organ type. For example, lung transplants have a long-term success rate of around 59%, while kidney transplants fare better at 82%, liver transplants at 80%, and heart transplants at 73%. These statistics underscore the challenge: the need for constant monitoring to detect rejection early and to take corrective action before it's too late.

The Challenge of Monitoring Rejection

For decades, doctors have been trying to find a way to identify organ rejection early, when intervention can be most effective. The problem is that many transplant recipients show no outward symptoms of rejection, making it difficult to detect unless a biopsy is performed. Biopsies, however, are invasive, expensive, and not always conclusive.

As a result, transplant patients live with a constant sense of uncertainty and anxiety, never knowing whether their body is rejecting the organ. This is especially true for kidney transplant patients, the most common organ transplant recipients. As Northwestern Medicine transplant nephrologist Dr. Lorenzo Gallon explains, "I have noticed many of my patients feel constant anxiety—not knowing if their body is rejecting their transplanted organ or not."

While blood and urine tests have been used to monitor some types of rejection, these methods have often been unreliable and limited to specific organs. To date, there has been no universal test that works across all types of organ transplants.

The Breakthrough: Non-Invasive Blood Test for Organ Rejection

In a groundbreaking new study, a team of researchers led by statistician Harry Robertson from the University of Sydney has identified a set of biomarkers that could revolutionize transplant monitoring. This discovery provides the first evidence that biomarkers of dysfunction can be identified across multiple organ types, including kidneys, livers, hearts, and lungs. These biomarkers are detectable in blood samples, offering a non-invasive way to predict organ rejection before it leads to severe damage.

The researchers analyzed 54 datasets, which included 40 studies on kidney transplants, 5 on lung transplants, 5 on liver transplants, and 4 on heart transplants. By comparing individual patient blood samples to their biopsy results, the team identified 158 genes that were consistently expressed during rejection episodes across all four organs. This number is nearly 20 times higher than what would be expected by chance, making the discovery all the more remarkable.

What Do These Biomarkers Tell Us?

These biomarkers are involved in several key processes related to immune response and cell death. Some of the genes are associated with proteins that stimulate white blood cells, enzymes that trigger cell death, receptors on cells that regulate material transport, and bone marrow cells involved in immune responses. By monitoring these biomarkers, doctors could gain a much clearer picture of whether a transplanted organ is facing rejection, and how severe the rejection may be.

Robertson and his team have coined this discovery as a "unifying pan-organ molecular marker," meaning that these biomarkers could be used to predict rejection across various types of organ transplants. Unlike other models that are currently in development and focused on a single organ, Robertson’s method outperformed these organ-specific models by providing a broader, more consistent predictive tool.

Study Reference: https://www.nature.com/articles/s41591-024-03030-6

The Implications for Transplant Medicine

This discovery holds enormous potential for improving transplant outcomes. By developing a blood test based on these biomarkers, doctors could diagnose rejection in its earliest stages, allowing for earlier intervention. Early detection could lead to more effective treatments, reducing the need for invasive procedures like biopsies and preventing the need for additional transplants.

Furthermore, the discovery could lead to personalized treatment strategies based on the specific type of rejection occurring. For example, different biomarkers could be used to differentiate between immune-mediated rejection, rejection due to inadequate blood supply, or maladaptive repair processes that interfere with the healing of the transplanted organ.

The ability to predict organ rejection at such an early stage could also improve patient confidence. As Dr. Gallon notes, many transplant patients live in a state of constant uncertainty, worrying whether their body is rejecting their transplanted organ. A reliable blood test would allow doctors to provide more clarity and reduce anxiety for these patients.

Potential for Universal Blood Test

Although the study is still in its early stages, the potential for a universal blood test to predict organ rejection is significant. The team has already developed an interactive website that allows researchers and scientists to compare potential biomarkers of transplant rejection with other existing methods. This platform is crucial for standardizing the evaluation of biomarkers and could lead to the development of a universally accepted test for organ rejection.

Robertson believes that this work could set a new standard in precision medicine, a field that focuses on tailoring medical treatment to individual patients based on their genetic, environmental, and lifestyle factors. By using blood tests to predict transplant rejection, doctors could customize treatments to suit the specific needs of each patient, improving both the efficacy and efficiency of transplant care.

Next Steps and Challenges

While the discovery is promising, there are still several challenges that need to be addressed before a universal blood test becomes available for clinical use. For one, the team has yet to test their findings on other types of organ transplants, such as pancreas, stomach, and intestine transplants. Additionally, more research is needed to confirm the reliability of these biomarkers across a larger population of transplant recipients.

The research also needs to be validated through clinical trials to determine whether it can be effectively used in real-world settings. While the biomarkers have shown promise in lab studies, they will need to be tested in a variety of clinical conditions to ensure that they accurately predict rejection and can be integrated into existing medical practices.

Despite these hurdles, the potential impact of this research on transplant medicine is immense. With further development, this discovery could lead to a future where organ rejection is no longer a silent threat, but something that can be detected and treated before it becomes life-threatening.