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Early post-lung transplant cell-free DNA levels are associated with baseline lung allograft dysfunction
Andrea Zajacova1, Majd Alkhouri1, Goncalo Ferrao2
1Prague Lung Transplant Program, Department of Pneumology, Second Faculty of Medicine, Charles University, Motol University Hospital, V Uvalu 84, 150 06 Prague, Czechia.
Background:
Baseline lung allograft dysfunction (BLAD) is defined as the failure to achieve normal pulmonary function-specifically, forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) values of ≥80 %-within the first year after lung transplantation. It is hypothesised that early subclinical injury, reflected by elevated donor-derived cell-free DNA (dd-cfDNA), both in absolute concentration and percentage (dd-cfDNA%), as well as total cell-free DNA (cfDNA), may be predictive of subsequent BLAD development.
Methods:
We included patients who underwent bilateral lung transplantation between May 2021 and September 2023. Blood samples collected between 3 and 9 months post-transplantation were analysed for dd-cfDNA%, dd-cfDNA concentration (copies/mL), and estimated total cfDNA (copies/mL). BLAD was defined by failure to achieve both FEV₁ and FVC ≥80 % of predicted values within the first year.
Results:
A total of 158 samples from 37 patients were analysed. Ten patients (27 %) met the BLAD criteria. Those with BLAD had significantly higher dd-cfDNA levels (median: 39 cp/mL) compared to non-BLAD patients (26 cp/mL; p = 0.01). Similarly, total cfDNA levels were significantly elevated in the BLAD group (22,809 cp/mL vs. 13,840 cp/mL; p = 0.002). However, dd-cfDNA% did not differ significantly (0.23 % vs. 0.15 %; p = 0.2).
Conclusion:
Elevated absolute dd-cfDNA and total cfDNA levels in the early post-transplant period were associated with BLAD, suggesting that cfDNA may serve as a potential predictive biomarker. These findings support the potential of cfDNA-based biomarkers to enhance early detection of graft dysfunction, warranting validation in larger cohorts.
