Cell-free DNA as a biomarker after lung transplantation: A proof-of-concept study

Background: Lung transplantation (LTx) is a lifesaving procedure burdened with limited long-term survival. The most common cause of death after LTx is chronic lung allograft dysfunction (CLAD). Today, useful biomarkers for the detection of CLAD are lacking. Circulating cell-free DNA (cfDNA) is released during cellular decay and can be detected using polymerase chain reaction (PCR). Thus, donor-derived cfDNA in recipient serum indicates cellular decay in the transplanted organ. In the current study, we explore the possibility of using a novel PCR method to detect cfDNA as a biomarker for clinical events, especially CLAD. Methods: Four patients were retrospectively tested for levels of both donor and recipient-derived cfDNA using digital droplet PCR after targeted preamplification. The results were correlated to recorded clinical events. Results: All available samples rendered results. Both patients that later developed CLAD showed a persistently elevated ratio between donor-and recipient-derived cfDNA. Also, the mean level of cfDNA was higher in the two patients who later developed CLAD than in patients who did not (p = .0015). Conclusions: This proof-of-concept study suggests that cfDNA quantified with PCR may be used as a biomarker of significant clinical events such as CLAD.