(992) Platelet Transcriptome As a Liquid Biopsy for Acute Cellular Rejection after Heart Transplantation

PurposePlatelets may sequester free RNA and could therefore be used as a biomarker for monitoring of allografts after transplantation. The purpose of this study is to address the correspondent usability of platelets as a liquid biopsy to distinguish recipients with acutely rejecting allografts from recipients with healthy allografts.MethodsWe prospectively collected recipient peripheral blood platelets and endomyocardial biopsies (EMB) from 50 recipients at the time of surveillance biopsies during the first year after transplantation (at 2, 4, 6, and 8 weeks, at 3, 4, 5, 6, 8, 10, and 12 months, and at time of clinically suspected acute rejection). EMB were analyzed for degree of acute cell- and antibody-mediated rejection and fibrosis. Platelet RNA was isolated with mirVana miRNA isolation kit (Invitrogen). The 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.ResultsPreliminary results on a small data set showed that the platelet transcriptome mirrored the occurrence (Figure 1) as well as the severity (Figure 2) of acute cellular rejection episodes.ConclusionAnalysis of the platelet transcriptome has the potential to replace the expensive and invasive technique of taking EMB with a more feasible and cost-effective liquid blood biopsy. The final results comprising the whole patient cohort will be presented at the ISHLT 2023 meeting. Platelets may sequester free RNA and could therefore be used as a biomarker for monitoring of allografts after transplantation. The purpose of this study is to address the correspondent usability of platelets as a liquid biopsy to distinguish recipients with acutely rejecting allografts from recipients with healthy allografts. We prospectively collected recipient peripheral blood platelets and endomyocardial biopsies (EMB) from 50 recipients at the time of surveillance biopsies during the first year after transplantation (at 2, 4, 6, and 8 weeks, at 3, 4, 5, 6, 8, 10, and 12 months, and at time of clinically suspected acute rejection). EMB were analyzed for degree of acute cell- and antibody-mediated rejection and fibrosis. Platelet RNA was isolated with mirVana miRNA isolation kit (Invitrogen). The 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. Preliminary results on a small data set showed that the platelet transcriptome mirrored the occurrence (Figure 1) as well as the severity (Figure 2) of acute cellular rejection episodes. Analysis of the platelet transcriptome has the potential to replace the expensive and invasive technique of taking EMB with a more feasible and cost-effective liquid blood biopsy. The final results comprising the whole patient cohort will be presented at the ISHLT 2023 meeting.