Sustained Molecular Allograft Injury After Episodes of Acute Rejection and Organizing Pneumonia Increases the Risk of Lung Allograft Failure
Background. Despite treatment of major risk factors such as acute rejection (AR) and organizing pneumonia (OP) in lung transplant recipients, chronic lung allograft dysfunction (CLAD) still develops at high rates, suggesting that traditional methods of assessing response to treatment and resolution...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer
2025-07-01
|
| Series: | Transplantation Direct |
| Online Access: | http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001828 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850067606241804288 |
|---|---|
| author | Michael B. Keller, MD Allison Y. Lin Moon Kyoo Jang, PhD Hyesik Kong, PhD Ananth Charya, MD Gerald J. Berry, MD Charles C. Marboe, MD Ileana L. Ponor, MD, MBA Shambhu Aryal, MD Jonathan B. Orens, MD Pali D. Shah, MD Steven D. Nathan, MD Xin Tian, PhD Sean Agbor-Enoh, MD, PhD |
| author_facet | Michael B. Keller, MD Allison Y. Lin Moon Kyoo Jang, PhD Hyesik Kong, PhD Ananth Charya, MD Gerald J. Berry, MD Charles C. Marboe, MD Ileana L. Ponor, MD, MBA Shambhu Aryal, MD Jonathan B. Orens, MD Pali D. Shah, MD Steven D. Nathan, MD Xin Tian, PhD Sean Agbor-Enoh, MD, PhD |
| author_sort | Michael B. Keller, MD |
| collection | DOAJ |
| description | Background. Despite treatment of major risk factors such as acute rejection (AR) and organizing pneumonia (OP) in lung transplant recipients, chronic lung allograft dysfunction (CLAD) still develops at high rates, suggesting that traditional methods of assessing response to treatment and resolution remain inadequate. It is unknown whether the degree of molecular allograft injury after treatment of AR/OP modulates the risk of CLAD and death.
Methods. To evaluate the association of molecular allograft injury after AR/OP with the incidence of CLAD/death, we conducted a multicenter prospective cohort study that included 93 patients who underwent lung transplantation between 2015 and 2022. The degree of molecular allograft injury after AR/OP was quantified by the mean area under the curve of longitudinal measures of plasma donor-derived cell-free DNA (dd-cfDNA).
Results. Over a median follow-up of 5 y, patients who developed CLAD/death had persistently higher levels of dd-cfDNA in the months after AR/OP. In multivariable Cox regression analysis adjusting for patient and transplant risk factors, mean dd-cfDNA levels after AR/OP were independently associated with an increased risk of CLAD/death (adjusted hazard ratio, 2.84; 95% confidence interval, 1.67-4.83; P < 0.001) and remained consistent when accounting for changes in pulmonary function after AR/OP events (hazard ratio, 2.62; 95% confidence interval, 1.53-4.47; P < 0.001).
Conclusions. The degree of allograft injury on the molecular level after AR/OP events in lung transplant recipients is associated with the risk of developing CLAD or death. This study demonstrates the potential of dd-cfDNA for improving risk stratification and monitoring the resolution and treatment responses of lung allograft injury. |
| format | Article |
| id | doaj-art-016e466a1cfb4052bd0b93d05e2bfca6 |
| institution | DOAJ |
| issn | 2373-8731 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Transplantation Direct |
| spelling | doaj-art-016e466a1cfb4052bd0b93d05e2bfca62025-08-20T02:48:16ZengWolters KluwerTransplantation Direct2373-87312025-07-01117e182810.1097/TXD.0000000000001828202507000-00009Sustained Molecular Allograft Injury After Episodes of Acute Rejection and Organizing Pneumonia Increases the Risk of Lung Allograft FailureMichael B. Keller, MD0Allison Y. Lin1Moon Kyoo Jang, PhD2Hyesik Kong, PhD3Ananth Charya, MD4Gerald J. Berry, MD5Charles C. Marboe, MD6Ileana L. Ponor, MD, MBA7Shambhu Aryal, MD8Jonathan B. Orens, MD9Pali D. Shah, MD10Steven D. Nathan, MD11Xin Tian, PhD12Sean Agbor-Enoh, MD, PhD131 Division of Pulmonary, Critical Care & Sleep Medicine, University of Maryland Medical Center, Baltimore, MD.4 Laboratory of Applied Precision Omics (APO), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.3 Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD.3 Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD.1 Division of Pulmonary, Critical Care & Sleep Medicine, University of Maryland Medical Center, Baltimore, MD.3 Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD.3 Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD.3 Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD.3 Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD.3 Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD.3 Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD.3 Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD.4 Laboratory of Applied Precision Omics (APO), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.3 Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD.Background. Despite treatment of major risk factors such as acute rejection (AR) and organizing pneumonia (OP) in lung transplant recipients, chronic lung allograft dysfunction (CLAD) still develops at high rates, suggesting that traditional methods of assessing response to treatment and resolution remain inadequate. It is unknown whether the degree of molecular allograft injury after treatment of AR/OP modulates the risk of CLAD and death. Methods. To evaluate the association of molecular allograft injury after AR/OP with the incidence of CLAD/death, we conducted a multicenter prospective cohort study that included 93 patients who underwent lung transplantation between 2015 and 2022. The degree of molecular allograft injury after AR/OP was quantified by the mean area under the curve of longitudinal measures of plasma donor-derived cell-free DNA (dd-cfDNA). Results. Over a median follow-up of 5 y, patients who developed CLAD/death had persistently higher levels of dd-cfDNA in the months after AR/OP. In multivariable Cox regression analysis adjusting for patient and transplant risk factors, mean dd-cfDNA levels after AR/OP were independently associated with an increased risk of CLAD/death (adjusted hazard ratio, 2.84; 95% confidence interval, 1.67-4.83; P < 0.001) and remained consistent when accounting for changes in pulmonary function after AR/OP events (hazard ratio, 2.62; 95% confidence interval, 1.53-4.47; P < 0.001). Conclusions. The degree of allograft injury on the molecular level after AR/OP events in lung transplant recipients is associated with the risk of developing CLAD or death. This study demonstrates the potential of dd-cfDNA for improving risk stratification and monitoring the resolution and treatment responses of lung allograft injury.http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001828 |
| spellingShingle | Michael B. Keller, MD Allison Y. Lin Moon Kyoo Jang, PhD Hyesik Kong, PhD Ananth Charya, MD Gerald J. Berry, MD Charles C. Marboe, MD Ileana L. Ponor, MD, MBA Shambhu Aryal, MD Jonathan B. Orens, MD Pali D. Shah, MD Steven D. Nathan, MD Xin Tian, PhD Sean Agbor-Enoh, MD, PhD Sustained Molecular Allograft Injury After Episodes of Acute Rejection and Organizing Pneumonia Increases the Risk of Lung Allograft Failure Transplantation Direct |
| title | Sustained Molecular Allograft Injury After Episodes of Acute Rejection and Organizing Pneumonia Increases the Risk of Lung Allograft Failure |
| title_full | Sustained Molecular Allograft Injury After Episodes of Acute Rejection and Organizing Pneumonia Increases the Risk of Lung Allograft Failure |
| title_fullStr | Sustained Molecular Allograft Injury After Episodes of Acute Rejection and Organizing Pneumonia Increases the Risk of Lung Allograft Failure |
| title_full_unstemmed | Sustained Molecular Allograft Injury After Episodes of Acute Rejection and Organizing Pneumonia Increases the Risk of Lung Allograft Failure |
| title_short | Sustained Molecular Allograft Injury After Episodes of Acute Rejection and Organizing Pneumonia Increases the Risk of Lung Allograft Failure |
| title_sort | sustained molecular allograft injury after episodes of acute rejection and organizing pneumonia increases the risk of lung allograft failure |
| url | http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001828 |
| work_keys_str_mv | AT michaelbkellermd sustainedmolecularallograftinjuryafterepisodesofacuterejectionandorganizingpneumoniaincreasestheriskoflungallograftfailure AT allisonylin sustainedmolecularallograftinjuryafterepisodesofacuterejectionandorganizingpneumoniaincreasestheriskoflungallograftfailure AT moonkyoojangphd sustainedmolecularallograftinjuryafterepisodesofacuterejectionandorganizingpneumoniaincreasestheriskoflungallograftfailure AT hyesikkongphd sustainedmolecularallograftinjuryafterepisodesofacuterejectionandorganizingpneumoniaincreasestheriskoflungallograftfailure AT ananthcharyamd sustainedmolecularallograftinjuryafterepisodesofacuterejectionandorganizingpneumoniaincreasestheriskoflungallograftfailure AT geraldjberrymd sustainedmolecularallograftinjuryafterepisodesofacuterejectionandorganizingpneumoniaincreasestheriskoflungallograftfailure AT charlescmarboemd sustainedmolecularallograftinjuryafterepisodesofacuterejectionandorganizingpneumoniaincreasestheriskoflungallograftfailure AT ileanalponormdmba sustainedmolecularallograftinjuryafterepisodesofacuterejectionandorganizingpneumoniaincreasestheriskoflungallograftfailure AT shambhuaryalmd sustainedmolecularallograftinjuryafterepisodesofacuterejectionandorganizingpneumoniaincreasestheriskoflungallograftfailure AT jonathanborensmd sustainedmolecularallograftinjuryafterepisodesofacuterejectionandorganizingpneumoniaincreasestheriskoflungallograftfailure AT palidshahmd sustainedmolecularallograftinjuryafterepisodesofacuterejectionandorganizingpneumoniaincreasestheriskoflungallograftfailure AT stevendnathanmd sustainedmolecularallograftinjuryafterepisodesofacuterejectionandorganizingpneumoniaincreasestheriskoflungallograftfailure AT xintianphd sustainedmolecularallograftinjuryafterepisodesofacuterejectionandorganizingpneumoniaincreasestheriskoflungallograftfailure AT seanagborenohmdphd sustainedmolecularallograftinjuryafterepisodesofacuterejectionandorganizingpneumoniaincreasestheriskoflungallograftfailure |