Platelet Transcriptome as a Liquid Biopsy for Rejection After Heart Transplantation

Abstract

<h3>Purpose</h3> "Tumor-educated" platelets that have exchanged nucleic acids and proteins with tumor cells have been shown to enable the discrimination of tumor patients from healthy individuals. We hypothesize that platelets could perform the same function in the setting of organ transplantation, i.e., be useful as a biomarker to distinguish recipients with rejecting allografts from recipients with healthy allografts. The goal would be to replace the expensive and invasive technique of taking endomyocardial biopsies with a more feasible and cost-effective liquid blood biopsy. <h3>Methods</h3> We have prospectively collected recipient platelets and endomyocardial biopsies from 50 recipients at 2, 4, 6, and 8 weeks, and at 3, 4, 5, 6, 8, 10, and 12 months after transplantation, as well as at any time of suspected acute rejection. Endomyocardial biopsies have been analyzed for degree of acute cell- and antibody-mediated rejection and fibrosis. Platelet RNA has been isolated with mirVana miRNA isolation kit (Invitrogen), and the RNA from myocardial biopsies with RNeasy microkit (Qiagen). Whole transcriptome sequencing will be performed on an Illumina Novaseq platform. The sequenced data will be processed bioinformatically for a detailed molecular comparison of the platelet transcriptome with endomyocardial biopsies and the clinical data of the patient. <h3>Endpoints</h3> The aim is to discover potential biomarkers to predict the development of heart allograft rejection by analysis of differential gene expression patterns in platelets. The results of the preliminary experiment will be presented at the ISHLT 2022 meeting. Should the approach be successful, the results will be confirmed and extended with samples from a larger cohort.