AUTHOR=Beeckmans H. , Pagliazzi A. , Kerckhof P. , Hofkens R. , Debackere F. , Zajacova A. , Bos S. , Vanaudenaerde B. M. , de Loor H. , Naesens M. , Vos R. 

TITLE=Donor-derived cell-free DNA in chronic lung allograft dysfunction phenotypes: a pilot study

JOURNAL=Frontiers in Transplantation

VOLUME=Volume 3 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/transplantation/articles/10.3389/frtra.2024.1513101

DOI=10.3389/frtra.2024.1513101

ISSN=2813-2440

ABSTRACT=Long-term survival after lung transplantation is limited due to chronic lung allograft dysfunction (CLAD), which encompasses two main phenotypes: bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). Donor-derived cell-free DNA (dd-cfDNA) is a biomarker for (sub)clinical allograft injury and could be a tool for monitoring of lung allograft health across the (pre)clinical spectrum of CLAD. In this proof-of-concept study, we therefore assessed post-transplant plasma dd-cfDNA levels in 20 CLAD patients (11 BOS and 9 RAS) at three consecutive time points free from concurrent infection or acute rejection, during stable condition, preclinical CLAD, and established CLAD (n = 3 × 20 samples). Elevated dd-cfDNA levels were detected in 47% of stable samples, in 66% of preclinical CLAD samples, and in 71% of CLAD samples, indicating ongoing allograft injury. However, dd-cfDNA levels exhibited high intra- and interpatient variability and did not significantly differ between BOS and RAS (p = 0.25), although the range of dd-cfDNA was higher in RAS. Dd-cfDNA detects ongoing allograft injury in patients with CLAD, which warrants further investigation to improve early detection of CLAD.