Although more patients are now surviving longer after lung transplantation, chronic allograft dysfunction due to ACR and AMR still remains a significant risk factor. Invasive histopathology of transbronchial biopsies is the method of choice for the detection of acute rejection. The aim of this study is to investigate the potential utility of donor-derived cell-free DNA (ddcfDNA) as a non-invasive biomarker for the detection of allograft function and acute rejection after lung transplantation

Home made digital droplet PCR was used to determine the total amount of cell-free DNA as well as the total amount and the proportion of ddcfDNA. In 81 lung recipients from whom blood was taken before and several times after transplantation, median levels of ddcfDNA [%] was related to cellular or humoral rejection, infection or changes in lung function (Wilcoxon and Kruskal-Wallis test).

70.4 % of the patients were male and had a mean age of 55.4 years (sd=11.0). The most common underlying disease was ILD (55.6%), followed by COPD (18.5%) and rheumatic diseases (13.6%). The probability of acute rejection was significantly higher in pre-immunised patients (75.0% vs. 30.1%, p=0.02). The patient group with ACR (1.92, IQR:0.70-2.30), AMR (1.27, IQR:0.34-2.29), isolated lymphocytic bronchiolitis (0.54, IQR:0.23-2.18) and infection (0.50, IQR: 0.22-2.35) had significantly increased mean %ddcfDNA values compared to the cohort with healthy allograft function (0.26, IQR:0.09-0.60) (p=0.0003). Patients with FEV1 loss had significantly higher %ddcfDNA values (1.98, IQR:0.50-2.30, p=0.04) compared to patients with stable or improving lung function at 12 months (1.36, IQR:0.27-1.66).

These results suggest that ddcfDNA is a promising biomarker for monitoring allograft function to detect allograft damage caused by ACR, AMR or infection at an early stage. Finally, this non-invasive biomarker could help to reduce the number of biopsies in the future.

no conflict of interest