Simple Blood Test Could Replace Biopsies for Lung Transplant Rejection Monitoring

These procedures can cause complications such as bleeding or air leaks and add burden to patients and care teams. Identifying a reliable, noninvasive biomarker for early rejection has remained elusive. A new study shows that a blood-based approach targeting T cell small extracellular vesicles may enable earlier detection of rejection after lung transplantation.

Yale School of Medicine (New Haven, CT, USA) researchers, with collaborators at Washington University School of Medicine (St. Louis, MO, USA), evaluated a platform that isolates and enriches T cell–derived small extracellular vesicles (sEVs) from whole blood. The approach exploits the role of T cells as primary drivers of acute cellular rejection (ACR). By extracting extracellular vesicles and preferentially enriching those from T cells, the platform interrogates immune activation signatures that reflect early rejection biology.

The team first studied mouse models of lung transplantation. Seven days after transplant, investigators compared circulating sEV profiles between animals with ACR and those without, observing deviations that correlated with lung tissue changes associated with rejection. They then assessed the platform in 20 patients who underwent bilateral lung transplantation, analyzing blood samples collected one, three, and 30 days after surgery.

In patients who experienced ACR, T cell sEVs showed changes similar to those observed in the animal models, indicating concordant biology across species. The findings, published in the American Journal of Transplantation, suggest that targeted analysis of T cell sEVs can distinguish individuals with early rejection from those without. The investigators noted plans to validate the technology in a larger cohort over a longer follow-up to compare performance against biopsy-based monitoring.

“Globally there’s a need for better diagnostics in transplant patients that allow us to intervene earlier when less damage is done to the organ, which we believe predisposes patients to chronic rejection,” said Daniel Kreisel, MD, PhD, the G. Alexander Patterson MD / Mid-America Transplant Endowed Distinguished Chair in Lung Transplantation and surgical director of lung transplantation at Washington University School of Medicine and the study’s co-principal investigator.

“We could very well be on our way to having a novel blood test that can replace or minimize having to do biopsies for lung transplant monitoring,” said Prashanth Vallabhajosyula, MD, professor of surgery (cardiac) at Yale School of Medicine and the study’s co-principal investigator.

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