Dataset Information

Cell-free DNA in the surveillance of heart transplant rejection.

ABSTRACT:

Background

Circulating cell-free deoxyribonucleic acid (cfDNA) is promptly materializing as a highly useful tool for the surveillance of solid-organ transplant rejection. Donor-specific fraction (DF) cfDNA is a potential marker of selective donor organ injury. It is emerging as a promising analytical target in the near future. The aim of this systematic review is to throw light on the importance of cfDNA and future perspective in detecting acute rejection in heart transplantation.

Methods

An exhaustive search was carried out for this review article on the basis of literature available including scientific databases of PubMed, Embase, and ClinicalTrials.gov. The search engines were systematically explored using the search terms "cell free DNA," "Heart transplant," and "Rejection" from inception until August 2020, and narrative analysis was accomplished. Majority of the studies described endomyocardial biopsy-proven acute rejection as reference standard.

Results

After initial screening of 331 articles, 11 studies were included and discussed in detail in the present review article. Majority of the studies showed prospective designs. A firm correlation was noted between acute rejection (identified on endomyocardial biopsy) and cfDNA levels by most of the studies.

Conclusions

cfDNA is a promising tool to replace repeated biopsies to detect rejection. The development in the area of digital droplet polymerase chain reaction and massive parallel sequencing, along with the overall reduction in cost of sequencing with its automation, has helped establish its role in the transplant population.

SUBMITTER: Sharma D

PROVIDER: S-EPMC8079572 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Publications

Cell-free DNA in the surveillance of heart transplant rejection.

Sharma Dhruva D Subramaniam Ganapathy G Sharma Neha N Sharma Preksha P

Indian journal of thoracic and cardiovascular surgery 20210202 3

<h4>Background</h4>Circulating cell-free deoxyribonucleic acid (cfDNA) is promptly materializing as a highly useful tool for the surveillance of solid-organ transplant rejection. Donor-specific fraction (DF) cfDNA is a potential marker of selective donor organ injury. It is emerging as a promising analytical target in the near future. The aim of this systematic review is to throw light on the importance of cfDNA and future perspective in detecting acute rejection in heart transplantation.<h4>Met ...[more]

PMID: 33967413

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Project description:BackgroundAfter heart transplantation, endomyocardial biopsy (EMBx) is used to monitor for acute rejection (AR). Unfortunately, EMBx is invasive, and its conventional histological interpretation has limitations. This is a validation study to assess the performance of a sensitive blood biomarker-percent donor-derived cell-free DNA (%ddcfDNA)-for detection of AR in cardiac transplant recipients.MethodsThis multicenter, prospective cohort study recruited heart transplant subjects and collected plasma samples contemporaneously with EMBx for %ddcfDNA measurement by shotgun sequencing. Histopathology data were collected to define AR, its 2 phenotypes (acute cellular rejection [ACR] and antibody-mediated rejection [AMR]), and controls without rejection. The primary analysis was to compare %ddcfDNA levels (median and interquartile range [IQR]) for AR, AMR, and ACR with controls and to determine %ddcfDNA test characteristics using receiver-operator characteristics analysis.ResultsThe study included 171 subjects with median posttransplant follow-up of 17.7 months (IQR, 12.1-23.6), with 1392 EMBx, and 1834 %ddcfDNA measures available for analysis. Median %ddcfDNA levels decayed after surgery to 0.13% (IQR, 0.03%-0.21%) by 28 days. Also, %ddcfDNA increased again with AR compared with control values (0.38% [IQR, 0.31-0.83%], versus 0.03% [IQR, 0.01-0.14%]; P<0.001). The rise was detected 0.5 and 3.2 months before histopathologic diagnosis of ACR and AMR. The area under the receiver operator characteristic curve for AR was 0.92. A 0.25%ddcfDNA threshold had a negative predictive value for AR of 99% and would have safely eliminated 81% of EMBx. In addition, %ddcfDNA showed distinctive characteristics comparing AMR with ACR, including 5-fold higher levels (AMR ≥2, 1.68% [IQR, 0.49-2.79%] versus ACR grade ≥2R, 0.34% [IQR, 0.28-0.72%]), higher area under the receiver operator characteristic curve (0.95 versus 0.85), higher guanosine-cytosine content, and higher percentage of short ddcfDNA fragments.ConclusionsWe found that %ddcfDNA detected AR with a high area under the receiver operator characteristic curve and negative predictive value. Monitoring with ddcfDNA demonstrated excellent performance characteristics for both ACR and AMR and led to earlier detection than the EMBx-based monitoring. This study supports the use of %ddcfDNA to monitor for AR in patients with heart transplant and paves the way for a clinical utility study. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02423070.

Dataset Information

Cell-free DNA in the surveillance of heart transplant rejection.

Background

Methods

Results

Conclusions

Publications

Cell-free DNA in the surveillance of heart transplant rejection.

Similar Datasets

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