AUTHOR=Sorbini Monica , Togliatto Gabriele , Mioli Fiorenza , Simonato Erika , Marro Matteo , Cappuccio Margherita , Arruga Francesca , Caorsi Cristiana , Mansouri Morteza , Magistroni Paola , Gambella Alessandro , Delsedime Luisa , Papotti Mauro Giulio , Solidoro Paolo , Albera Carlo , Boffini Massimo , Rinaldi Mauro , Amoroso Antonio , Vaisitti Tiziana , 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/journals/transplant-international/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.