Platelet Transcriptome As A Biomarker For Rejection After Heart Transplantation

Purpose: “Tumor-educated” platelets that have exchanged nucleic acids and proteins with tumor cells have been shown to be useful for the discrimination of tumor patients from healthy individuals (Best et al., 2015). We hypothesize that platelets could yield similar information in the setting of organ transplantation, i.e., be used as a biomarker to distinguish recipients with rejecting allografts from recipients with healthy allografts. This could be a way to replace the expensive and invasive technique of taking endomyocardial biopsies for monitoring transplanted allografts with a better sufferable and more cost-effective liquid blood biopsy. Methods: We are currently collecting platelets and endomyocardial biopsies from heart transplant 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. Platelet RNA will be isolated with mirVana miRNA isolation kit (Invitrogen), RNA from biopsies with RNeasy minikit (Qiagen). Whole transcriptome sequencing will be performed on an Illumina Novaseq platform. Bioinformatical processing of the sequenced data will provide a detailed molecular comparison of the endomyocardial biopsy transcriptome with the platelet transcriptome and the clinical data of the patient. Endpoints: The goal is to discover potential biomarkers for onset and development of heart allograft rejection by analysis of differential gene expression patterns in platelets. The results of the preliminary experiment will be presented on the TTS 2020 congress. Should the approach be successful, the results will be confirmed with samples from a larger cohort. Reference: 1. Best et al., Cancer Cell. 2015;28:666-676