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Comparing plasma donor-derived cell-free DNA to gene expression in endomyocardial biopsies in the Trifecta-Heart Study

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F24%3A00085027" target="_blank" >RIV/00023001:_____/24:00085027 - isvavai.cz</a>

  • Result on the web

    <a href="https://journals.lww.com/transplantjournal/fulltext/2024/09000/comparing_plasma_donor_derived_cell_free_dna_to.14.aspx" target="_blank" >https://journals.lww.com/transplantjournal/fulltext/2024/09000/comparing_plasma_donor_derived_cell_free_dna_to.14.aspx</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1097/TP.0000000000004986" target="_blank" >10.1097/TP.0000000000004986</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Comparing plasma donor-derived cell-free DNA to gene expression in endomyocardial biopsies in the Trifecta-Heart Study

  • Original language description

    Background. Plasma donor-derived cell-free DNA (dd-cfDNA) is used to screen for rejection in heart transplants. We launched the Trifecta-Heart study (ClinicalTrials.gov No. NCT04707872), an investigator-initiated, prospective trial, to examine the correlations between genome-wide molecular changes in endomyocardial biopsies (EMBs) and plasma dd-cfDNA. The present report analyzes the correlation of plasma dd-cfDNA with gene expression in EMBs from 4 vanguard centers and compared these correlations with those in 604 kidney transplant biopsies in the Trifecta-Kidney study (ClinicalTrials.gov No. NCT04239703). Methods. We analyzed 137 consecutive dd-cfDNA-EMB pairs from 70 patients. Plasma %dd-cfDNA was measured by the Prospera test (Natera Inc), and gene expression in EMBs was assessed by Molecular Microscope Diagnostic System using machine-learning algorithms to interpret rejection and injury states. Results. Top transcripts correlating with dd-cfDNA were related to genes increased in rejection such as interferon gamma-inducible genes (eg, HLA-DMA) but also with genes induced by injury and expressed in macrophages (eg, SERPINA1 and HMOX1). In gene enrichment analysis, the top dd-cfDNA-correlated genes reflected inflammation and rejection pathways. Dd-cfDNA correlations with rejection genes in EMB were similar to those seen in kidney transplant biopsies, with somewhat stronger correlations for TCMR genes in hearts and ABMR genes in kidneys. However, the correlations with parenchymal injury-induced genes and macrophage genes were much stronger in hearts. Conclusions. In this first analysis of Trifecta-Heart study, dd-cfDNA correlates significantly with molecular rejection but also with injury and macrophage infiltration, reflecting the proinflammatory properties of injured cardiomyocytes. The relationship supports the utility of dd-cfDNA in clinical management of heart transplant recipients.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30201 - Cardiac and Cardiovascular systems

Result continuities

  • Project

  • Continuities

    N - Vyzkumna aktivita podporovana z neverejnych zdroju

Others

  • Publication year

    2024

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Transplantation

  • ISSN

    0041-1337

  • e-ISSN

    1534-6080

  • Volume of the periodical

    108

  • Issue of the periodical within the volume

    9

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    12

  • Pages from-to

    1931-1942

  • UT code for WoS article

    001281353100067

  • EID of the result in the Scopus database

    2-s2.0-85197922603