Blood Test Detects Organ Rejection in Heart Transplant Patients

Rejection happens when the recipient’s immune system identifies the transplanted heart as foreign and launches an immune response against it. The most frequent form of rejection is acute cellular rejection, which involves immune cells known as T cells. This condition is categorized into mild, moderate, or severe grades. Mild rejection usually doesn’t show symptoms, though some patients might experience vague, flu-like signs.

In more serious cases, symptoms can include an irregular or rapid heartbeat, low blood pressure, dizziness, and difficulty breathing. Through tissue biopsies, pathologists can detect rejection by examining the presence of T cells and evaluating the level of damage they inflict on the transplanted heart. The assigned grade informs the appropriate course of treatment. In cases of moderate or severe rejection found via biopsy, doctors typically increase immunosuppressive medication to reverse it, whereas mild rejection is often just monitored. However, there is currently no reliable, noninvasive method to verify whether treatment is effective.

Since therapies differ for acute cellular rejection and antibody-mediated rejection, a diagnostic test capable of detecting and distinguishing between these types would be invaluable for guiding treatment decisions. Conducting heart biopsies carries risks, prompting researchers over the years to search for alternative biomarkers that could replace invasive procedures. Most episodes of acute cellular rejection occur within the first six months post-transplant. Unfortunately, the limited blood tests available today are not effective at identifying rejection during the crucial initial 30 days. A less invasive method to monitor immune activity would be transformative for transplant recipients. Researchers now point to a promising biomarker that could make it possible to replace surgical biopsies with a simple blood test.

Over the past decade, scientists at the Yale School of Medicine (YSM, New Haven, CT, USA) have been investigating exosomes as a potential biomarker for heart transplant rejection in animal studies. Cells use exosomes—tiny biological packages filled with molecules—to communicate and transfer information. A new study published in the journal Transplantation marks a major step in translating this research from animal models to human heart transplant patients, potentially introducing biomarker testing into clinical practice. In this study, blood samples were collected from 12 heart transplant patients before and after surgery, and researchers analyzed the molecular contents of exosomes released by T cells, B cells, and the transplanted donor heart. Six patients experienced a total of 11 episodes of moderate acute cellular rejection. When the heart was not being attacked by T cells, the team observed specific patterns of molecular content in the exosomes from the heart and T cells. However, when rejection occurred, they detected increased levels of markers linked to the rejection process.

Importantly, one patient experienced a different type of rejection known as antibody-mediated rejection, which primarily involves B cells, aided by T cells. By analyzing the exosomes from that patient’s B cells, researchers were also able to detect this form of rejection. Of the 11 total rejection episodes recorded in the study, 10 occurred within the first 38 days after transplant, and researchers successfully identified all of them. When patients received treatment for rejection, the molecular signatures in exosomes from T cells and donor heart cells shifted back toward their baseline levels. The team at YSM is now expanding their research by analyzing biopsy samples from more than 100 patients. With this larger group, they aim to further evaluate their platform’s effectiveness in detecting different types of rejection, including antibody-mediated cases.

“Not only can we detect rejection, but our investigation also suggests that we can use our exosome platform to potentially monitor the efficacy of treatment of rejection,” said principal investigator Prashanth Vallabhajosyula, MD, who led the research team.

“This is the first time that we’ve had a noninvasive method to delineate between the different types of rejection that may occur within the heart,” added study co-author Sounok Sen, MD.