@ARTICLE{10.3389/ti.2022.10546, AUTHOR={Sorbini, Monica and Togliatto, Gabriele and Mioli, Fiorenza and Simonato, Erika and Marro, Matteo and Cappuccio, Margherita and Arruga, Francesca and Caorsi, Cristiana and Mansouri, Morteza and Magistroni, Paola and Gambella, Alessandro and Delsedime, Luisa and Papotti, Mauro Giulio and Solidoro, Paolo and Albera, Carlo and Boffini, Massimo and Rinaldi, Mauro and Amoroso, Antonio and Vaisitti, Tiziana and Deaglio, Silvia}, TITLE={Validation of a Simple, Rapid, and Cost-Effective Method for Acute Rejection Monitoring in Lung Transplant Recipients}, JOURNAL={Transplant International}, VOLUME={35}, YEAR={2022}, URL={https://www.frontierspartnerships.org/articles/10.3389/ti.2022.10546}, DOI={10.3389/ti.2022.10546}, ISSN={1432-2277}, ABSTRACT={Despite advances in immunosuppression therapy, acute rejection remains the leading cause of graft dysfunction in lung transplant recipients. Donor-derived cell-free DNA is increasingly being considered as a valuable biomarker of acute rejection in several solid organ transplants. We present a technically improved molecular method based on digital PCR that targets the mismatch between the recipient and donor at the HLA-DRB1 locus. Blood samples collected sequentially post-transplantation from a cohort of lung recipients were used to obtain proof-of-principle for the validity of the assay, correlating results with transbronchial biopsies and lung capacity tests. The results revealed an increase in dd-cfDNA during the first 2 weeks after transplantation related to ischemia-reperfusion injury (6.36 ± 5.36%, p < 0.0001). In the absence of complications, donor DNA levels stabilized, while increasing again during acute rejection episodes (7.81 ± 12.7%, p < 0.0001). Respiratory tract infections were also involved in the release of dd-cfDNA (9.14 ± 15.59%, p = 0.0004), with a positive correlation with C-reactive protein levels. Overall, the dd-cfDNA percentages were inversely correlated with the lung function values measured by spirometry. These results confirm the value of dd-cfDNA determination during post-transplant follow-up to monitor acute rejection in lung recipients, achieved using a rapid and inexpensive approach based on the HLA mismatch between donor and recipient.} }