Exosomes: A Promising Biomarker for Cellular Rejection After Organ Transplant

Good news! Sounds promising! Seems to be an impressive study (from a layman's perspective)!

"Today, patients who receive an organ transplant need repeated surgical biopsies to test for acute cellular rejection (ACR) throughout their lifetimes. But a blood test for ACR could be on the horizon following the discovery of a promising biomarker. ...
Now, a Yale team has found that exosomes from T cells are significantly altered during ACR. Exosomes are extracellular vesicles released by cells that allow them to communicate with each other. ...
However, even when these patients are on immunosuppressants, breakthrough cases of rejection can still occur. ...
However, there is a significant challenge to studying T cell exosomes: A sample of blood contains exosomes from every cell type in the body. ...
his lab has developed a way to enrich T cell exosomes in biological samples to give his team an unparalleled look into how their cargo changes during ACR. ...

In their latest study, the researchers took blood samples from mouse models of heart transplantation and isolated all the exosomes. Then, they used antibody-conjugated bead technology — in which antibodies attached to magnetic beads bind to target molecules — to isolate T cell exosomes. This allowed them to quantify this specific exosome population and study the cargo inside it. They used a technique called quantitative reverse transcription polymerase chain reaction (RT-qPCR) to identify RNAs and the western blot technique for proteins.

The team discovered dramatic differences in the content of T cell exosomes taken from mouse models undergoing ACR. ..."

From the abstract:

There is a critical need for biomarkers of acute cellular rejection (ACR) in organ transplantation. We hypothesized that ACR leads to changes in donor-reactive T cell small extracellular vesicle (sEV) profiles in transplant recipient circulation that match the kinetics of alloreactive T cell activation. In rodent heart transplantation, circulating T cell sEV quantities (P < .0001) and their protein and mRNA cargoes showed time-specific expression of alloreactive and regulatory markers heralding early ACR in allogeneic transplant recipients but not in syngeneic transplant recipients. Next generation sequencing of their microRNA cargoes identified novel candidate biomarkers of ACR, which were validated by stem loop quantitative reverse transcription polymerase chain reaction (n = 10). Circulating T cell sEVs enriched from allogeneic transplant recipients mediated targeted cytotoxicity of donor cardiomyocytes by apoptosis assay (P < .0001). Translation of the concept and EV methodologies to clinical heart transplantation demonstrated similar upregulation of circulating T cell sEV profiles at time points of grade 2 ACR (n = 3 patients). Furthermore, T cell receptor sequencing of T cell sEV mRNA cargo demonstrated expression of T cell clones with intact complementarity determining region 3 signals. These data support the diagnostic potential of T cell sEVs as noninvasive biomarker of ACR and suggest their potential functional roles."

Exosomes: A Promising Biomarker for Cellular Rejection After Organ Transplant < Yale School of Medicine

Circulating T cell specific extracellular vesicle profiles in cardiac allograft acute cellular rejection (no public access)