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Photo credit: istock.com/ks Kim
Studies have shown that small extracellular vesicles washed away by donor cardiac cells and circulating T cells provide an accurate reading of heart transplant rejection.
Although routine endofascial biopsies remain the gold standard for rating acute cell rejection (ACR) after heart transplantation, new studies published in transplantation show that donor cardiac cells (SEVs) drain and T cells circulating T cells provide accurate and minimal invasive reads of rejection.
“T cells constantly monitor the environment, looking for infections and other things that are “non-self,” says a news release that looks for Yale School of Medicine Prashanth Vallabhajosyula, MD, MPH, MPH, MPH, MPH, MPH, MPH, MPH, in a news release. “They consider the implanted heart non-self, so they attack them.”
Clear molecular shift signal risk
In a longitudinal pilot study, the investigators collected 70 pairs of blood samples and biopsies from 12 recipients in the first 120 days after the operation. They isolated donor-derived SEVs with anti-human leukocyte antigen (HLA) I beads and probed with cardiac troponin T (CTNT) protein and messenger ribonucleic acid (mRNA). (mRNA) let-7i, 101b, and 21a.
Research findings showed that 11 episodes of moderate ACR occurred in six patients (incidence rate of 15.7%). Compared to grade 0/1 biopsies, donor-heartcebu CTNT protein and mRNA were significantly reduced (P <0.001), and T cell SEV protein and miRNA cargo were elevated (all P <0.001). These shifts were detectable as early as 5 days after implantation. According to the author, 10 of the 11 episodes presented within 38 days were presented within 38 days.
Surveillance treatment success
By escalating immunosuppression, the researchers reversed both clinical rejection and SEV signatures. Donor-Hart CTNT mRNA and miR-21A followed treatment response using Spearman coefficients of 0.87 and 0.85, respectively.
“In addition to detecting rejections, our research suggests that exosome platforms can potentially monitor the effectiveness of treatments for rejection,” Vallabhajosyula said. The authors also noted that the platform identified one case of antibody-mediated rejection by analyzing B-cell SEVs, highlighting its versatility.
Towards safer transplant care
“This is the first time there has been a non-invasive method to depict the different types of rejection that can occur within the heart,” says Sounok Sen, MD, a research co-author at Yale School of Medicine.
According to the researchers, a larger validation study is currently underway involving more than 100 patients to improve diagnostic thresholds and assess long-term prognostic value. They noted that if confirmed, SEV profiling could significantly reduce the need for repeated biopsies, reducing the need for reduced procedural complications, allowing clinicians to adjust treatment more quickly, and ultimately improve outcomes for heart transplant recipients.
