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Donor-Specific Cell-Free DNA qPCR Quantification as a Noninvasive Accurate Biomarker for Early Rejection Detection in Liver Transplantation

(1) Background: Graft-cell-free DNA (cfDNA) in the circulation of liver transplant recipients has been proposed as a noninvasive biomarker of organ rejection. The aim of this study was to detect donor-specific cfDNA (ds-cfDNA) in the recipient’s serum after either liver damage or rejection using a q...

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Autores principales: García-Fernández, Noelia, Macher, Hada C., Suárez-Artacho, Gonzalo, Gómez-Bravo, Miguel Ángel, Molinero, Patrocinio, Guerrero, Juan Miguel, Porras-López, Manuel, Rubio, Amalia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821236/
https://www.ncbi.nlm.nih.gov/pubmed/36614837
http://dx.doi.org/10.3390/jcm12010036
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author García-Fernández, Noelia
Macher, Hada C.
Suárez-Artacho, Gonzalo
Gómez-Bravo, Miguel Ángel
Molinero, Patrocinio
Guerrero, Juan Miguel
Porras-López, Manuel
Rubio, Amalia
author_facet García-Fernández, Noelia
Macher, Hada C.
Suárez-Artacho, Gonzalo
Gómez-Bravo, Miguel Ángel
Molinero, Patrocinio
Guerrero, Juan Miguel
Porras-López, Manuel
Rubio, Amalia
author_sort García-Fernández, Noelia
collection PubMed
description (1) Background: Graft-cell-free DNA (cfDNA) in the circulation of liver transplant recipients has been proposed as a noninvasive biomarker of organ rejection. The aim of this study was to detect donor-specific cfDNA (ds-cfDNA) in the recipient’s serum after either liver damage or rejection using a qPCR-based method. (2) Methods: We proposed a qPCR method based on the amplification of 10 specific insertion–deletion (InDel) polymorphisms to detect donor-specific circulating DNA diluted in the recipient cfDNA. ds-cfDNA from 67 patients was evaluated during the first month post-transplantation. (3) Results: Graft rejection in the first month post-transplantation was reported in 13 patients. Patients without liver complications showed a transitory increase in ds-cfDNA levels at transplantation. Patients with rejection showed significant differences in ds-cfDNA increase over basal levels at both the rejection time point and several days before rejection. Receiver operator characteristic (ROC) analysis showed that ds-cfDNA levels discriminated rejection, with an AUC of 0.96. Maximizing both sensitivity and specificity, a threshold cutoff of 8.6% provided an estimated positive and negative predictive value of 99% and 60%, respectively. (4) Conclusions: These results suggest that ds-cfDNA may be a useful marker of graft integrity in liver transplant patients to screen for rejection and liver damage.
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spelling pubmed-98212362023-01-07 Donor-Specific Cell-Free DNA qPCR Quantification as a Noninvasive Accurate Biomarker for Early Rejection Detection in Liver Transplantation García-Fernández, Noelia Macher, Hada C. Suárez-Artacho, Gonzalo Gómez-Bravo, Miguel Ángel Molinero, Patrocinio Guerrero, Juan Miguel Porras-López, Manuel Rubio, Amalia J Clin Med Article (1) Background: Graft-cell-free DNA (cfDNA) in the circulation of liver transplant recipients has been proposed as a noninvasive biomarker of organ rejection. The aim of this study was to detect donor-specific cfDNA (ds-cfDNA) in the recipient’s serum after either liver damage or rejection using a qPCR-based method. (2) Methods: We proposed a qPCR method based on the amplification of 10 specific insertion–deletion (InDel) polymorphisms to detect donor-specific circulating DNA diluted in the recipient cfDNA. ds-cfDNA from 67 patients was evaluated during the first month post-transplantation. (3) Results: Graft rejection in the first month post-transplantation was reported in 13 patients. Patients without liver complications showed a transitory increase in ds-cfDNA levels at transplantation. Patients with rejection showed significant differences in ds-cfDNA increase over basal levels at both the rejection time point and several days before rejection. Receiver operator characteristic (ROC) analysis showed that ds-cfDNA levels discriminated rejection, with an AUC of 0.96. Maximizing both sensitivity and specificity, a threshold cutoff of 8.6% provided an estimated positive and negative predictive value of 99% and 60%, respectively. (4) Conclusions: These results suggest that ds-cfDNA may be a useful marker of graft integrity in liver transplant patients to screen for rejection and liver damage. MDPI 2022-12-21 /pmc/articles/PMC9821236/ /pubmed/36614837 http://dx.doi.org/10.3390/jcm12010036 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
García-Fernández, Noelia
Macher, Hada C.
Suárez-Artacho, Gonzalo
Gómez-Bravo, Miguel Ángel
Molinero, Patrocinio
Guerrero, Juan Miguel
Porras-López, Manuel
Rubio, Amalia
Donor-Specific Cell-Free DNA qPCR Quantification as a Noninvasive Accurate Biomarker for Early Rejection Detection in Liver Transplantation
title Donor-Specific Cell-Free DNA qPCR Quantification as a Noninvasive Accurate Biomarker for Early Rejection Detection in Liver Transplantation
title_full Donor-Specific Cell-Free DNA qPCR Quantification as a Noninvasive Accurate Biomarker for Early Rejection Detection in Liver Transplantation
title_fullStr Donor-Specific Cell-Free DNA qPCR Quantification as a Noninvasive Accurate Biomarker for Early Rejection Detection in Liver Transplantation
title_full_unstemmed Donor-Specific Cell-Free DNA qPCR Quantification as a Noninvasive Accurate Biomarker for Early Rejection Detection in Liver Transplantation
title_short Donor-Specific Cell-Free DNA qPCR Quantification as a Noninvasive Accurate Biomarker for Early Rejection Detection in Liver Transplantation
title_sort donor-specific cell-free dna qpcr quantification as a noninvasive accurate biomarker for early rejection detection in liver transplantation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821236/
https://www.ncbi.nlm.nih.gov/pubmed/36614837
http://dx.doi.org/10.3390/jcm12010036
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