• Something wrong with this record ?

Comparing Plasma Donor-derived Cell-free DNA to Gene Expression in Endomyocardial Biopsies in the Trifecta-Heart Study

PF. Halloran, J. Reeve, M. Mackova, KS. Madill-Thomsen, Z. Demko, M. Olymbios, P. Campbell, V. Melenovsky, T. Gong, S. Hall, J. Stehlik

. 2024 ; 108 (9) : 1931-1942. [pub] 20240820

Language English Country United States

Document type Journal Article, Comparative Study, Multicenter Study

Persistent link   https://www.medvik.cz/link/bmc24019201

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.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc24019201
003      
CZ-PrNML
005      
20241024111426.0
007      
ta
008      
241015s2024 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1097/TP.0000000000004986 $2 doi
035    __
$a (PubMed)38538559
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Halloran, Philip F $u Alberta Transplant Applied Genomics Center, Edmonton, AB, Canada $u Department of Medicine, University of Alberta, Edmonton, AB, Canada $u Transcriptome Sciences Inc, Edmonton, AB, Canada
245    10
$a Comparing Plasma Donor-derived Cell-free DNA to Gene Expression in Endomyocardial Biopsies in the Trifecta-Heart Study / $c PF. Halloran, J. Reeve, M. Mackova, KS. Madill-Thomsen, Z. Demko, M. Olymbios, P. Campbell, V. Melenovsky, T. Gong, S. Hall, J. Stehlik
520    9_
$a 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.
650    _2
$a lidé $7 D006801
650    12
$a transplantace srdce $x škodlivé účinky $7 D016027
650    12
$a volné cirkulující nukleové kyseliny $x krev $x genetika $7 D000073888
650    12
$a rejekce štěpu $x genetika $x imunologie $x patologie $x krev $x diagnóza $7 D006084
650    _2
$a prospektivní studie $7 D011446
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a biopsie $7 D001706
650    _2
$a lidé středního věku $7 D008875
650    12
$a dárci tkání $7 D014019
650    12
$a myokard $x patologie $x metabolismus $7 D009206
650    _2
$a dospělí $7 D000328
650    _2
$a transplantace ledvin $x škodlivé účinky $7 D016030
650    _2
$a biologické markery $x krev $7 D015415
650    _2
$a senioři $7 D000368
650    _2
$a stanovení celkové genové exprese $7 D020869
650    _2
$a prediktivní hodnota testů $7 D011237
655    _2
$a časopisecké články $7 D016428
655    _2
$a srovnávací studie $7 D003160
655    _2
$a multicentrická studie $7 D016448
700    1_
$a Reeve, Jeff $u Alberta Transplant Applied Genomics Center, Edmonton, AB, Canada $u Transcriptome Sciences Inc, Edmonton, AB, Canada
700    1_
$a Mackova, Martina $u Alberta Transplant Applied Genomics Center, Edmonton, AB, Canada $u Transcriptome Sciences Inc, Edmonton, AB, Canada
700    1_
$a Madill-Thomsen, Katelynn S $u Alberta Transplant Applied Genomics Center, Edmonton, AB, Canada $u Transcriptome Sciences Inc, Edmonton, AB, Canada
700    1_
$a Demko, Zachary $u Natera Inc, San Carlos, CA
700    1_
$a Olymbios, Michael $u Natera Inc, San Carlos, CA
700    1_
$a Campbell, Patrick $u Baptist Health Institute, Little Rock, AR
700    1_
$a Melenovsky, Vojtech $u IKEM, Prague, Czech Republic
700    1_
$a Gong, Timothy $u Baylor Scott & White Health, Dallas, TX
700    1_
$a Hall, Shelley $u Baylor Scott & White Health, Dallas, TX
700    1_
$a Stehlik, Josef $u Department of Internal Medicine, University of Utah, Salt Lake City, UT
773    0_
$w MED00010695 $t Transplantation $x 1534-6080 $g Roč. 108, č. 9 (2024), s. 1931-1942
856    41
$u https://pubmed.ncbi.nlm.nih.gov/38538559 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20241015 $b ABA008
991    __
$a 20241024111420 $b ABA008
999    __
$a ok $b bmc $g 2201817 $s 1231174
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2024 $b 108 $c 9 $d 1931-1942 $e 20240820 $i 1534-6080 $m Transplantation $n Transplantation $x MED00010695
LZP    __
$a Pubmed-20241015

Find record

Citation metrics

Archiving options