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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30201 - Cardiac and Cardiovascular systems

Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Transplantation

ISSN

0041-1337

e-ISSN

1534-6080

Svazek periodika

108

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

1931-1942

Kód UT WoS článku

001281353100067

EID výsledku v databázi Scopus

2-s2.0-85197922603