Increased Donor‐Derived Cell‐Free DNA as a Predictor for the Early Detection of Antibody‐Mediated Rejection Following Heart Transplantation

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Autores principales: Dana Dlouha, Sarka Chytilova, Jevgenija Vymetalova, Eva Rohlova, Marianna Lukasova, Sarka Novakova, Jaroslav Alois Hubacek
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Publicado: Wiley 2025
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author Dana Dlouha
Sarka Chytilova
Jevgenija Vymetalova
Eva Rohlova
Marianna Lukasova
Sarka Novakova
Jaroslav Alois Hubacek
author_facet Dana Dlouha
Sarka Chytilova
Jevgenija Vymetalova
Eva Rohlova
Marianna Lukasova
Sarka Novakova
Jaroslav Alois Hubacek
Dana Dlouha
Sarka Chytilova
Jevgenija Vymetalova
Eva Rohlova
Marianna Lukasova
Sarka Novakova
Jaroslav Alois Hubacek
collection Wiley Open Access
contents Increased Donor‐Derived Cell‐Free DNA as a Predictor for the Early Detection of Antibody‐Mediated Rejection Following Heart Transplantation Dana Dlouha Sarka Chytilova Jevgenija Vymetalova Eva Rohlova Marianna Lukasova Sarka Novakova Jaroslav Alois Hubacek Clinical Transplantation ABSTRACT Plasma circulating donor‐derived cell‐free DNA (ddcfDNA) can be used to noninvasively monitor acute rejection of heart transplants (HTx). This study utilized digital droplet PCR to analyze ddcfDNA concentrations (measured in copies per milliliter) and the fractional abundance (%ddcfDNA) to differentiate between donor and recipient DNA on the basis of single nucleotide polymorphism (SNP) homozygosity. Seventy‐seven patients participated in a study, providing 300 plasma samples. Both markers, mean ddcfDNA (cp/mL) and %ddcfDNA, showed similar decreasing trends following the HTx, ( R 2  < 0.2; p  < 0.001). Significantly higher levels of ddcfDNA (cp/mL) and %ddcfDNA were observed during episodes of acute rejection (AR) compared to non‐rejection samples ( p  < 0.001). Additionally, antibody‐mediated rejection (AMR) was associated with increased %ddcfDNA levels compared to non‐rejection and to acute cellular rejection samples ( p  < 0.001 and p  < 0.01). A logistic regression model identified %ddcfDNA as an early predictor of AMR risk 10–19 days post‐heart transplant (odds ratio 158, p  < 0.02). Performance analysis established an optimal %ddcfDNA threshold of 0.125% for AMR detection, correctly identifying all patients without subsequent AMR. These findings suggest that early %ddcfDNA measurements post‐HTx can accurately identify individuals unlikely to develop AMR during the first posttransplant year. 10.1111/ctr.70209 http://onlinelibrary.wiley.com/termsAndConditions#vor
doi_str_mv 10.1111/ctr.70209
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publisher Wiley
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spellingShingle Increased Donor‐Derived Cell‐Free DNA as a Predictor for the Early Detection of Antibody‐Mediated Rejection Following Heart Transplantation
Dana Dlouha
Sarka Chytilova
Jevgenija Vymetalova
Eva Rohlova
Marianna Lukasova
Sarka Novakova
Jaroslav Alois Hubacek
Clinical Transplantation
Increased Donor‐Derived Cell‐Free DNA as a Predictor for the Early Detection of Antibody‐Mediated Rejection Following Heart Transplantation Dana Dlouha Sarka Chytilova Jevgenija Vymetalova Eva Rohlova Marianna Lukasova Sarka Novakova Jaroslav Alois Hubacek Clinical Transplantation ABSTRACT Plasma circulating donor‐derived cell‐free DNA (ddcfDNA) can be used to noninvasively monitor acute rejection of heart transplants (HTx). This study utilized digital droplet PCR to analyze ddcfDNA concentrations (measured in copies per milliliter) and the fractional abundance (%ddcfDNA) to differentiate between donor and recipient DNA on the basis of single nucleotide polymorphism (SNP) homozygosity. Seventy‐seven patients participated in a study, providing 300 plasma samples. Both markers, mean ddcfDNA (cp/mL) and %ddcfDNA, showed similar decreasing trends following the HTx, ( R 2  < 0.2; p  < 0.001). Significantly higher levels of ddcfDNA (cp/mL) and %ddcfDNA were observed during episodes of acute rejection (AR) compared to non‐rejection samples ( p  < 0.001). Additionally, antibody‐mediated rejection (AMR) was associated with increased %ddcfDNA levels compared to non‐rejection and to acute cellular rejection samples ( p  < 0.001 and p  < 0.01). A logistic regression model identified %ddcfDNA as an early predictor of AMR risk 10–19 days post‐heart transplant (odds ratio 158, p  < 0.02). Performance analysis established an optimal %ddcfDNA threshold of 0.125% for AMR detection, correctly identifying all patients without subsequent AMR. These findings suggest that early %ddcfDNA measurements post‐HTx can accurately identify individuals unlikely to develop AMR during the first posttransplant year. 10.1111/ctr.70209 http://onlinelibrary.wiley.com/termsAndConditions#vor
title Increased Donor‐Derived Cell‐Free DNA as a Predictor for the Early Detection of Antibody‐Mediated Rejection Following Heart Transplantation
topic Clinical Transplantation
url https://onlinelibrary.wiley.com/doi/10.1111/ctr.70209