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.