AUTHOR=Calabrese Fiorella , Pezzuto Federica , Vedovelli Luca , De Chellis Cecilia , Lunardi Francesca , Loy Monica , Faccioli Eleonora , Vadori Marta , Biondini Davide , Marinello Serena , Braccioni Fausto , Meloni Federica , Schiavon Marco , Giraudo Chiara , Del Vecchio Claudia , Levine Deborah J. , Cozzi Emanuele , Rea Federico 

TITLE=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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1619771

DOI=10.3389/fimmu.2025.1619771

ISSN=1664-3224

ABSTRACT=IntroductionPlasma 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 multidisciplinary team approach. The usefulness of bronchoalveolar lavage (BAL) dd-cfDNA in complementing detection of allograft injury was also investigated.MethodsPlasma 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.ResultsPatients 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-cfDNA 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.DiscussionOur 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 integration of plasma dd-cfDNA with other post-transplant follow-up investigations may allow more sensitive diagnoses and appropriate graft injury management.