Diagnostic Blood Test for Cellular Rejection after Organ Transplant Could Replace Surgical Biopsies

Transplanted organs constantly face the risk of being rejected by the recipient's immune system which differentiates self from non-self using T cells and B cells. T cells are commonly associated with acute cellular rejection (ACR), where T cells attack the transplanted organ. To counteract this, organ transplant recipients must take immunosuppressive drugs indefinitely. Despite this, rejection episodes can still occur, necessitating long-term monitoring. Currently, ACR detection in transplant patients requires repeated surgical biopsies throughout their lives. These biopsies are vital for monitoring ACR and adjusting treatments accordingly, yet they diminish the patient's quality of life and can cause severe complications. Now, the discovery of a promising biomarker has paved the way for a blood test for ACR.

Researchers at Yale School of Medicine (New Haven, CT, USA) have achieved a potential breakthrough in monitoring ACR via blood tests by focusing on T cell exosomes, which are significantly altered during ACR. These extracellular vesicles play a crucial role in cell communication and transport various proteins and RNAs. Although T cells themselves do not show detectable changes in the bloodstream during ACR, their exosomes do. Isolating these exosomes for study presents challenges due to the mixture of exosomes from various cells in the blood. The research team has developed a method to enrich T cell exosomes from blood samples, providing detailed insights into the changes in their cargo during ACR. Using advanced techniques like RT-qPCR for RNA and western blot for protein analysis, they have identified significant differences in T cell exosomes from mouse models of heart transplantation undergoing ACR.

This methodology was also applied to human heart transplant patients, confirming similar alterations in T cell exosomes in the case of ACR patients. The study demonstrates that T cell exosomes not only indicate the occurrence of ACR but may also contribute to the damage in transplant rejection. The ongoing research aims to validate this biomarker in a larger cohort of heart transplant recipients and to extend the findings to lung transplant monitoring. Ultimately, this could lead to replacing invasive surgical biopsies with a simple blood test for detecting ACR, enhancing the quality of life and potentially saving more lives by facilitating timely interventions.

“I’m imagining a future in which a heart transplant patient could go once a month to a local [diagnostics] lab,” said Prashanth Vallabhajosyula, MD, MS, associate professor of surgery (cardiac) and the study’s principal investigator. “They don’t have to come to a cath lab and get a biopsy of their transplanted heart. They just go to a local lab, give a blood sample, and go home, and clinicians would receive molecular information about the overall immune health of the transplanted heart.”

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