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Validation of a Simple, Rapid, and Cost-Effective Method for Acute Rejection Monitoring in Lung Transplant Recipients
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 techni...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221674/ https://www.ncbi.nlm.nih.gov/pubmed/35755857 http://dx.doi.org/10.3389/ti.2022.10546 |
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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 |
author_facet | 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 |
author_sort | Sorbini, Monica |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9221674 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92216742022-06-24 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 Magistroni, Paola Gambella, Alessandro Delsedime, Luisa Papotti, Mauro Giulio Solidoro, Paolo Albera, Carlo Boffini, Massimo Rinaldi, Mauro Amoroso, Antonio Vaisitti, Tiziana Deaglio, Silvia Transpl Int Health Archive 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. Frontiers Media S.A. 2022-06-09 /pmc/articles/PMC9221674/ /pubmed/35755857 http://dx.doi.org/10.3389/ti.2022.10546 Text en Copyright © 2022 Sorbini, Togliatto, Mioli, Simonato, Marro, Cappuccio, Arruga, Caorsi, Mansouri, Magistroni, Gambella, Delsedime, Papotti, Solidoro, Albera, Boffini, Rinaldi, Amoroso, Vaisitti and Deaglio. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Health Archive 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 Validation of a Simple, Rapid, and Cost-Effective Method for Acute Rejection Monitoring in Lung Transplant Recipients |
title | Validation of a Simple, Rapid, and Cost-Effective Method for Acute Rejection Monitoring in Lung Transplant Recipients |
title_full | Validation of a Simple, Rapid, and Cost-Effective Method for Acute Rejection Monitoring in Lung Transplant Recipients |
title_fullStr | Validation of a Simple, Rapid, and Cost-Effective Method for Acute Rejection Monitoring in Lung Transplant Recipients |
title_full_unstemmed | Validation of a Simple, Rapid, and Cost-Effective Method for Acute Rejection Monitoring in Lung Transplant Recipients |
title_short | Validation of a Simple, Rapid, and Cost-Effective Method for Acute Rejection Monitoring in Lung Transplant Recipients |
title_sort | validation of a simple, rapid, and cost-effective method for acute rejection monitoring in lung transplant recipients |
topic | Health Archive |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221674/ https://www.ncbi.nlm.nih.gov/pubmed/35755857 http://dx.doi.org/10.3389/ti.2022.10546 |
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