(298) Role of Donor-Derived Cell-Free DNA in Chronic Lung Allograft Dysfunction, a Longitudinal Study

PurposeSurvival after lung transplantation (LT) is hampered by the development of chronic lung allograft dysfunction (CLAD). There is no treatment available to reverse CLAD once diagnosed, but early intervention could modify the progressive lung function decline. Thus, biomarkers are need for early detection of CLAD. High levels of donor derived cell-free DNA (ddcfDNA) have been described to precede acute cellar rejection and antibody mediated rejection diagnosis. The aim of this study is to assess if there is any association between ddcfDNA and chronic lung allograft dysfunction (CLAD).MethodsThis is a longitudinal study in which ddcfDNA levels were determined in 100 LT recipients at the 3rd, 6th, 9th, 12th, 24th and 36th month after LT. Firstly, real-time PCR was performed to detect an informative INDEL polymorphism for each donor/recipient pair. Secondly, levels of ddcfDNA were determined by quantifying the informative INDEL by digital PCR in the plasma of the recipient. Clinical data was collected during a three years follow-up to determine infections, antibody mediated and acute cellular rejection, and CLAD.ResultsGlobally, we noted an upward trend of ddcfDNA levels at 1, 2 and 3 years of follow-up when referred to 3 months. Levels of ddcfDNA were compared between CLAD and no CLAD patients at different time points, and a cut-off value of 1.86% at 12 months could identify those patients with higher probability of developing CLAD (Figure 1).ConclusionDetermine ddcfDNA levels in plasma could be a useful non-invasive biomarker for CLAD prediction. This study was partially funded by ISCIII ("PI17/01485"), co-funded by ERDF and SEPAR (552/2017). Survival after lung transplantation (LT) is hampered by the development of chronic lung allograft dysfunction (CLAD). There is no treatment available to reverse CLAD once diagnosed, but early intervention could modify the progressive lung function decline. Thus, biomarkers are need for early detection of CLAD. High levels of donor derived cell-free DNA (ddcfDNA) have been described to precede acute cellar rejection and antibody mediated rejection diagnosis. The aim of this study is to assess if there is any association between ddcfDNA and chronic lung allograft dysfunction (CLAD). This is a longitudinal study in which ddcfDNA levels were determined in 100 LT recipients at the 3rd, 6th, 9th, 12th, 24th and 36th month after LT. Firstly, real-time PCR was performed to detect an informative INDEL polymorphism for each donor/recipient pair. Secondly, levels of ddcfDNA were determined by quantifying the informative INDEL by digital PCR in the plasma of the recipient. Clinical data was collected during a three years follow-up to determine infections, antibody mediated and acute cellular rejection, and CLAD. Globally, we noted an upward trend of ddcfDNA levels at 1, 2 and 3 years of follow-up when referred to 3 months. Levels of ddcfDNA were compared between CLAD and no CLAD patients at different time points, and a cut-off value of 1.86% at 12 months could identify those patients with higher probability of developing CLAD (Figure 1). Determine ddcfDNA levels in plasma could be a useful non-invasive biomarker for CLAD prediction. This study was partially funded by ISCIII ("PI17/01485"), co-funded by ERDF and SEPAR (552/2017).