ORIGINAL RESEARCH article
Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1619771
Detection of Lung Allograft Injury through a Comprehensive Multidisciplinary Analysis of Donor-Derived Cell-Free DNA in plasma and bronchoalveolar lavage: A real-world single center experience
Provisionally accepted
Fiorella Calabrese1*
Federica Pezzuto1
Luca Vedovelli1
Cecilia De Chellis1
Francesca Lunardi1Monica Loy2
Eleonora Faccioli1Marta Vadori1
Davide Biondini1Serena Marinello2Fausto Braccioni2
Federica Meloni1
Marco Schiavon1
Chiara Giraudo1Claudia Del Vecchio2
Deborah Levine3
Emanuele Cozzi1
FEDERICO REA1- 1University of Padua, Padua, Italy
- 2University Hospital of Padua, Padua, Veneto, Italy
- 3Stanford University, Stanford, California, United States
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Introduction: Plasma donor-derived cell-free DNA (dd-cfDNA) is an emerging potential tool for diagnosing lung graft injury. This study explored the relevance of dd-cfDNA levels in different graft injuries thoroughly characterized after a well-established multi-specmultidisciplinaryialist team approach. The usefulness of bronchoalveolar lavage (BAL) dd-cfDNA in complementing detection of allograft injury was also investigated.Methods: Plasma dd-cfDNA was measured by next generation sequence on 127 samples from patients visited consecutively, contemporaneously with a systematic analysis of surveillance transbronchial biopsy by LASHA template, BAL analysis and immunological monitoring.Results: Patients with immunological injury exhibited the highest plasma dd-cfDNA levels (median 2.67%), with a sensitivity of 100% while patients with non-immunological insults showed a sensitivity of 28%. The combination of BAL with plasma dd-cfDNAs improved the sensitivity for detecting non-immunological injury from 28% to 71%. Random forest analysis showed that plasma dd-cfDNA >1% was among the most important variables in predicting death and chronic lung allograft dysfunction. Discussion: Our data suggests that plasma dd-cfDNA is a useful tool for immunological graft injury assessment. The performance of BAL dd-cf DNA needs to be validated on larger case series. The
Keywords: Donor-Derived Cell-Free DNA (dd-cfDNA), Lung Transplantation, Allograft injury, Bronchoalveolar lavage (BAL), Plasma biomarkers
Received: 28 Apr 2025; Accepted: 04 Aug 2025.
Copyright: © 2025 Calabrese, Pezzuto, Vedovelli, De Chellis, Lunardi, Loy, Faccioli, Vadori, Biondini, Marinello, Braccioni, Meloni, Schiavon, Giraudo, Vecchio, Levine, Cozzi and REA. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Fiorella Calabrese, University of Padua, Padua, Italy
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