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.

Validation of a Simple, Rapid, and Cost-Effective Method for Acute Rejection Monitoring in Lung Transplant Recipients

Sorbini, Monica;Togliatto, Gabriele;Mioli, Fiorenza;Simonato, Erika;Marro, Matteo;Cappuccio, Margherita;Arruga, Francesca;Caorsi, Cristiana;Mansouri, Morteza;Gambella, Alessandro;Papotti, Mauro Giulio;Solidoro, Paolo;Albera, Carlo;Boffini, Massimo;Rinaldi, Mauro;Amoroso, Antonio;Vaisitti, Tiziana;Deaglio, Silvia
2022-01-01

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.
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acute rejection; biomarker; cell free circulating DNA; droplet-digital PCR; lung transplantation; Cost-Benefit Analysis; Graft Rejection; Humans; Lung; Tissue Donors; Cell-Free Nucleic Acids; Transplant Recipients
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
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1871666
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