Donor-derived cell-free DNA as a new biomarker for cardiac allograft rejection: A prospective study (FreeDNA-CAR)

BACKGROUND: There is a long-standing need for a noninvasive biomarker that allows monitoring of cardiac allograft rejection, avoiding the need for periodic endomyocardial biopsies (EMB). METHODS: Multicenter, observational, prospective study, performed between 2019 and 2023 (NCT 04973943). All patie...

Descripción completa

Detalles Bibliográficos
Autores: Jiménez Blanco, Marta, Crespo Leiro, María G., García Cosío, María Dolores, Gómez Bueno, Manuel, López Vilella, Raquel, Ortiz Bautista, Carlos, Farrero, Marta, Zegrí Reiriz, Isabel, Díaz Molina, Beatriz, García Romero, Elena, Rangel Sousa, Diego, Salterain, Nahikari, Garrido Bravo, Iris, Segovia Cubero, Javier
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/221585
Acceso en línea:https://hdl.handle.net/2445/221585
Access Level:acceso abierto
Palabra clave:Marcadors bioquímics
Trasplantament cardíac
Rebuig (Biologia)
Biochemical markers
Heart transplantation
Graft rejection
id ES_247ef2efb344d9b2c3fa22a791927cb6
oai_identifier_str oai:diposit.ub.edu:2445/221585
network_acronym_str ES
network_name_str España
repository_id_str
spelling Donor-derived cell-free DNA as a new biomarker for cardiac allograft rejection: A prospective study (FreeDNA-CAR)Jiménez Blanco, MartaCrespo Leiro, María G.García Cosío, María DoloresGómez Bueno, ManuelLópez Vilella, RaquelOrtiz Bautista, CarlosFarrero, MartaZegrí Reiriz, IsabelDíaz Molina, BeatrizGarcía Romero, ElenaRangel Sousa, DiegoSalterain, NahikariGarrido Bravo, IrisSegovia Cubero, JavierMarcadors bioquímicsTrasplantament cardíacRebuig (Biologia)Biochemical markersHeart transplantationGraft rejectionBACKGROUND: There is a long-standing need for a noninvasive biomarker that allows monitoring of cardiac allograft rejection, avoiding the need for periodic endomyocardial biopsies (EMB). METHODS: Multicenter, observational, prospective study, performed between 2019 and 2023 (NCT 04973943). All patients underwent 7 per-protocol surveillance EMB during the first postheart transplantation year. Donor-derived cell-free DNA (dd-cfDNA) levels were determined before each EMB, using Next Generation Sequencing Technology (Allonext assay, Eurofins Genome). The primary end-point was the association between dd-cfDNA levels and the presence of acute cellular rejection (ACR) in EMB. RESULTS: The study included 206 patients from 12 centers, with 1,090 pairs of EMB/dd-cfDNA determinations available for analysis. EMB with ACR (n = 49) were associated with dd-cfDNA levels significantly higher than those without, median 0.189% (interquartilic range 0.05-0.70) vs 0.095% (0.04-0.23), p = 0.013. A dd-cfDNA threshold of 0.10% showed a negative predictive value for ACR of 97%. A statistically significant association between N-terminal prohormone of brain (NTProBNP) and dd-cfDNA was also found, with an increase of 0.007% dd-cfDNA (95% confidence interval 0.003-0.011) for every 500 units of NTproBNP, p 0.001. The combination of both biomarkers for diagnosis of ACR showed an area under the receiver operating characteristic (ROC) curve of 0.681, and this combined approach was significantly better than dd-cfDNA alone (area under the ROC curve 0.603), p = 0.016. Using a cut-off point of 0.10% for dd-cfDNA and 1,000 UI/ml for NTproBNP, negative predictive value increased to 98.1%. CONCLUSIONS: dd-cfDNA may be a useful biomarker to rule out significant ACR in a low-risk population. However, a dd-cfDNA value above normal threshold does not correlate robustly with the presence of disease. The combination with NTproBNP, a readily available biomarker, increased the discrimination power of dd-cfDNA alone. CLINICAL TRIAL NOTATION: Donor-derived Cell-Free DNA as a New Biomarker in Cardiac Acute Rejection, NCT 04973943. J Heart Lung Transplant 2025;44:560-569 (c) 2024 The Authors. Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Elsevier BV2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/221585Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/j.healun.2024.11.009The Journal of Heart and Lung Transplantation, 2024, vol. 44, num. 4, p. 560-569https://doi.org/10.1016/j.healun.2024.11.009cc-by-nc-nd (c) Jiménez Blanco et al., 2024http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2215852026-05-27T06:46:51Z
dc.title.none.fl_str_mv Donor-derived cell-free DNA as a new biomarker for cardiac allograft rejection: A prospective study (FreeDNA-CAR)
title Donor-derived cell-free DNA as a new biomarker for cardiac allograft rejection: A prospective study (FreeDNA-CAR)
spellingShingle Donor-derived cell-free DNA as a new biomarker for cardiac allograft rejection: A prospective study (FreeDNA-CAR)
Jiménez Blanco, Marta
Marcadors bioquímics
Trasplantament cardíac
Rebuig (Biologia)
Biochemical markers
Heart transplantation
Graft rejection
title_short Donor-derived cell-free DNA as a new biomarker for cardiac allograft rejection: A prospective study (FreeDNA-CAR)
title_full Donor-derived cell-free DNA as a new biomarker for cardiac allograft rejection: A prospective study (FreeDNA-CAR)
title_fullStr Donor-derived cell-free DNA as a new biomarker for cardiac allograft rejection: A prospective study (FreeDNA-CAR)
title_full_unstemmed Donor-derived cell-free DNA as a new biomarker for cardiac allograft rejection: A prospective study (FreeDNA-CAR)
title_sort Donor-derived cell-free DNA as a new biomarker for cardiac allograft rejection: A prospective study (FreeDNA-CAR)
dc.creator.none.fl_str_mv Jiménez Blanco, Marta
Crespo Leiro, María G.
García Cosío, María Dolores
Gómez Bueno, Manuel
López Vilella, Raquel
Ortiz Bautista, Carlos
Farrero, Marta
Zegrí Reiriz, Isabel
Díaz Molina, Beatriz
García Romero, Elena
Rangel Sousa, Diego
Salterain, Nahikari
Garrido Bravo, Iris
Segovia Cubero, Javier
author Jiménez Blanco, Marta
author_facet Jiménez Blanco, Marta
Crespo Leiro, María G.
García Cosío, María Dolores
Gómez Bueno, Manuel
López Vilella, Raquel
Ortiz Bautista, Carlos
Farrero, Marta
Zegrí Reiriz, Isabel
Díaz Molina, Beatriz
García Romero, Elena
Rangel Sousa, Diego
Salterain, Nahikari
Garrido Bravo, Iris
Segovia Cubero, Javier
author_role author
author2 Crespo Leiro, María G.
García Cosío, María Dolores
Gómez Bueno, Manuel
López Vilella, Raquel
Ortiz Bautista, Carlos
Farrero, Marta
Zegrí Reiriz, Isabel
Díaz Molina, Beatriz
García Romero, Elena
Rangel Sousa, Diego
Salterain, Nahikari
Garrido Bravo, Iris
Segovia Cubero, Javier
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Marcadors bioquímics
Trasplantament cardíac
Rebuig (Biologia)
Biochemical markers
Heart transplantation
Graft rejection
topic Marcadors bioquímics
Trasplantament cardíac
Rebuig (Biologia)
Biochemical markers
Heart transplantation
Graft rejection
description BACKGROUND: There is a long-standing need for a noninvasive biomarker that allows monitoring of cardiac allograft rejection, avoiding the need for periodic endomyocardial biopsies (EMB). METHODS: Multicenter, observational, prospective study, performed between 2019 and 2023 (NCT 04973943). All patients underwent 7 per-protocol surveillance EMB during the first postheart transplantation year. Donor-derived cell-free DNA (dd-cfDNA) levels were determined before each EMB, using Next Generation Sequencing Technology (Allonext assay, Eurofins Genome). The primary end-point was the association between dd-cfDNA levels and the presence of acute cellular rejection (ACR) in EMB. RESULTS: The study included 206 patients from 12 centers, with 1,090 pairs of EMB/dd-cfDNA determinations available for analysis. EMB with ACR (n = 49) were associated with dd-cfDNA levels significantly higher than those without, median 0.189% (interquartilic range 0.05-0.70) vs 0.095% (0.04-0.23), p = 0.013. A dd-cfDNA threshold of 0.10% showed a negative predictive value for ACR of 97%. A statistically significant association between N-terminal prohormone of brain (NTProBNP) and dd-cfDNA was also found, with an increase of 0.007% dd-cfDNA (95% confidence interval 0.003-0.011) for every 500 units of NTproBNP, p 0.001. The combination of both biomarkers for diagnosis of ACR showed an area under the receiver operating characteristic (ROC) curve of 0.681, and this combined approach was significantly better than dd-cfDNA alone (area under the ROC curve 0.603), p = 0.016. Using a cut-off point of 0.10% for dd-cfDNA and 1,000 UI/ml for NTproBNP, negative predictive value increased to 98.1%. CONCLUSIONS: dd-cfDNA may be a useful biomarker to rule out significant ACR in a low-risk population. However, a dd-cfDNA value above normal threshold does not correlate robustly with the presence of disease. The combination with NTproBNP, a readily available biomarker, increased the discrimination power of dd-cfDNA alone. CLINICAL TRIAL NOTATION: Donor-derived Cell-Free DNA as a New Biomarker in Cardiac Acute Rejection, NCT 04973943. J Heart Lung Transplant 2025;44:560-569 (c) 2024 The Authors. Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/221585
url https://hdl.handle.net/2445/221585
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.healun.2024.11.009
The Journal of Heart and Lung Transplantation, 2024, vol. 44, num. 4, p. 560-569
https://doi.org/10.1016/j.healun.2024.11.009
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Jiménez Blanco et al., 2024
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Jiménez Blanco et al., 2024
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier BV
publisher.none.fl_str_mv Elsevier BV
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869404703059607552
score 15.812429

Similares en LA Referencia