Platelet Transcriptome as a Marker for Rejection after Heart Transplantation

Abstract

OF OBJECTIVES: "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 ultimate goal would be to replace the expensive and invasive technique of taking endomyocardial biopsies with a better sufferable and more cost-effective liquid blood biopsy. METHODS: We are collecting recipient platelets and endomyocardial biopsies 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 a Illumina Novaseq platform. The sequenced data will be processed bioinformatically for a detailed molecular comparison of endomyocardial biopsies with the platelet transcriptome and clinical data of the patient. ENDPOINTS: The ultimate goal is to discover potential biomarkers for onset and development of heart allograft rejection by analysis of differential gene expression patterns. The results of the preliminary experiment will be presented on the ISHLT 2020 congress. Should the approach be proven successful, the results will be confirmed with samples from a larger cohort.