Donor-derived cell-free DNA for detection of acute rejection in lung transplant recipients
IntroductionAcute rejection is a significant risk factor for developing chronic lung allograft dysfunction. Current monitoring tools, transbronchial biopsies and HLA antibody determination, have limitations in detecting acute rejection. This study aims to explore the potential utility of donor-deriv...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1531774/full |
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| author | Gökce Yavuz Julia Walter Julia Walter Kaimo Hirv Oliver Wachter Andrea Dick Julia Kovacs Julia Zimmermann Olaf M. Glueck Maximilian Vorstandlechner Nicole Samm Jan M. Fertmann Wulf Sienel Sebastian Michel Sebastian Michel Michael Irlbeck Nikolaus Kneidinger Nikolaus Kneidinger Nikolaus Kneidinger Rudolf Hatz Rudolf Hatz Jürgen Behr Jürgen Behr Christian Schneider Christian Schneider Teresa Kauke Teresa Kauke |
| author_facet | Gökce Yavuz Julia Walter Julia Walter Kaimo Hirv Oliver Wachter Andrea Dick Julia Kovacs Julia Zimmermann Olaf M. Glueck Maximilian Vorstandlechner Nicole Samm Jan M. Fertmann Wulf Sienel Sebastian Michel Sebastian Michel Michael Irlbeck Nikolaus Kneidinger Nikolaus Kneidinger Nikolaus Kneidinger Rudolf Hatz Rudolf Hatz Jürgen Behr Jürgen Behr Christian Schneider Christian Schneider Teresa Kauke Teresa Kauke |
| author_sort | Gökce Yavuz |
| collection | DOAJ |
| description | IntroductionAcute rejection is a significant risk factor for developing chronic lung allograft dysfunction. Current monitoring tools, transbronchial biopsies and HLA antibody determination, have limitations in detecting acute rejection. This study aims to explore the potential utility of donor-derived cell-free DNA (ddcfDNA) as a non-invasive biomarker for detecting acute rejection in lung transplant recipients (LTR).MethodsWe developed a molecular method based on digital droplet PCR to determine the total amount and the proportion of ddcfDNA. Using blood samples collected sequentially post-transplant from a cohort of 81 LTR, we compared median levels of %ddcfDNA in patients with acute cellular rejection (ACR), antibody-mediated rejection (AMR), infection, or decline in pulmonary function (FEV1).ResultsMedian %ddcfDNA levels were significantly higher in groups with ACR (1.92% [0.70%, 2.30%], p=0.0006), AMR (1.27% [0.34%, 2.29%], p=0.0009), isolated lymphocytic bronchiolitis (0.54% [0.23%, 2.18%], p=0.03), and infection or prolonged ventilation over 30 days (0.50% [0.22%, 2.35%], p=0.005) versus stable allograft function group (0.26% [0.09%, 0.60%]). %ddcfDNA levels were also elevated in patients with FEV1 loss compared to those with stable or improving FEV1 after 12 months (1.98% vs. 1.36%, p=0.04). An optimal cut-off of 0.73% for %ddcfDNA was calculated to detect ACR and AMR with 80% specificity and 68% sensitivity.Discussion%ddcfDNA is a promising biomarker for identifying allograft injury due to acute rejection in LTR and could be a valuable tool for monitoring allograft health. |
| format | Article |
| id | doaj-art-5465f20c88f2493181123d7557dd97a2 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-5465f20c88f2493181123d7557dd97a22025-01-29T06:45:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15317741531774Donor-derived cell-free DNA for detection of acute rejection in lung transplant recipientsGökce Yavuz0Julia Walter1Julia Walter2Kaimo Hirv3Oliver Wachter4Andrea Dick5Julia Kovacs6Julia Zimmermann7Olaf M. Glueck8Maximilian Vorstandlechner9Nicole Samm10Jan M. Fertmann11Wulf Sienel12Sebastian Michel13Sebastian Michel14Michael Irlbeck15Nikolaus Kneidinger16Nikolaus Kneidinger17Nikolaus Kneidinger18Rudolf Hatz19Rudolf Hatz20Jürgen Behr21Jürgen Behr22Christian Schneider23Christian Schneider24Teresa Kauke25Teresa Kauke26Division of Thoracic Surgery, University Hospital, LMU Munich, Munich, GermanyDivision of Thoracic Surgery, University Hospital, LMU Munich, Munich, GermanyDepartment of Medicine V, University Hospital, LMU Munich, Munich, GermanyMVZ Martinsried, Martinsried, GermanyMVZ Martinsried, Martinsried, GermanyDivision of Transfusion Medicine, University Hospital, LMU Munich, Munich, GermanyDivision of Thoracic Surgery, University Hospital, LMU Munich, Munich, GermanyDivision of Thoracic Surgery, University Hospital, LMU Munich, Munich, GermanyDivision of Thoracic Surgery, University Hospital, LMU Munich, Munich, GermanyDivision of Thoracic Surgery, University Hospital, LMU Munich, Munich, GermanyDivision of Thoracic Surgery, University Hospital, LMU Munich, Munich, GermanyDivision of Thoracic Surgery, University Hospital, LMU Munich, Munich, GermanyDivision of Thoracic Surgery, University Hospital, LMU Munich, Munich, GermanyDepartment of Cardiac Surgery, University Hospital, LMU Munich, Munich, GermanyComprehensive Pneumology Center Munich, German Center for Lung Research (DZL), Munich, GermanyDepartment of Anesthesiology, University Hospital, LMU Munich, Munich, GermanyDepartment of Medicine V, University Hospital, LMU Munich, Munich, GermanyComprehensive Pneumology Center Munich, German Center for Lung Research (DZL), Munich, GermanyDivision of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, AustriaDivision of Thoracic Surgery, University Hospital, LMU Munich, Munich, GermanyComprehensive Pneumology Center Munich, German Center for Lung Research (DZL), Munich, GermanyDepartment of Medicine V, University Hospital, LMU Munich, Munich, GermanyComprehensive Pneumology Center Munich, German Center for Lung Research (DZL), Munich, GermanyDivision of Thoracic Surgery, University Hospital, LMU Munich, Munich, GermanyComprehensive Pneumology Center Munich, German Center for Lung Research (DZL), Munich, GermanyDivision of Thoracic Surgery, University Hospital, LMU Munich, Munich, GermanyTransplant Center, University Hospital, LMU Munich, Munich, GermanyIntroductionAcute rejection is a significant risk factor for developing chronic lung allograft dysfunction. Current monitoring tools, transbronchial biopsies and HLA antibody determination, have limitations in detecting acute rejection. This study aims to explore the potential utility of donor-derived cell-free DNA (ddcfDNA) as a non-invasive biomarker for detecting acute rejection in lung transplant recipients (LTR).MethodsWe developed a molecular method based on digital droplet PCR to determine the total amount and the proportion of ddcfDNA. Using blood samples collected sequentially post-transplant from a cohort of 81 LTR, we compared median levels of %ddcfDNA in patients with acute cellular rejection (ACR), antibody-mediated rejection (AMR), infection, or decline in pulmonary function (FEV1).ResultsMedian %ddcfDNA levels were significantly higher in groups with ACR (1.92% [0.70%, 2.30%], p=0.0006), AMR (1.27% [0.34%, 2.29%], p=0.0009), isolated lymphocytic bronchiolitis (0.54% [0.23%, 2.18%], p=0.03), and infection or prolonged ventilation over 30 days (0.50% [0.22%, 2.35%], p=0.005) versus stable allograft function group (0.26% [0.09%, 0.60%]). %ddcfDNA levels were also elevated in patients with FEV1 loss compared to those with stable or improving FEV1 after 12 months (1.98% vs. 1.36%, p=0.04). An optimal cut-off of 0.73% for %ddcfDNA was calculated to detect ACR and AMR with 80% specificity and 68% sensitivity.Discussion%ddcfDNA is a promising biomarker for identifying allograft injury due to acute rejection in LTR and could be a valuable tool for monitoring allograft health.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1531774/fullddcfDNAacute cellular rejectionantibody mediated rejectionallograft injurylung transplantationnon-invasive biomarker |
| spellingShingle | Gökce Yavuz Julia Walter Julia Walter Kaimo Hirv Oliver Wachter Andrea Dick Julia Kovacs Julia Zimmermann Olaf M. Glueck Maximilian Vorstandlechner Nicole Samm Jan M. Fertmann Wulf Sienel Sebastian Michel Sebastian Michel Michael Irlbeck Nikolaus Kneidinger Nikolaus Kneidinger Nikolaus Kneidinger Rudolf Hatz Rudolf Hatz Jürgen Behr Jürgen Behr Christian Schneider Christian Schneider Teresa Kauke Teresa Kauke Donor-derived cell-free DNA for detection of acute rejection in lung transplant recipients Frontiers in Immunology ddcfDNA acute cellular rejection antibody mediated rejection allograft injury lung transplantation non-invasive biomarker |
| title | Donor-derived cell-free DNA for detection of acute rejection in lung transplant recipients |
| title_full | Donor-derived cell-free DNA for detection of acute rejection in lung transplant recipients |
| title_fullStr | Donor-derived cell-free DNA for detection of acute rejection in lung transplant recipients |
| title_full_unstemmed | Donor-derived cell-free DNA for detection of acute rejection in lung transplant recipients |
| title_short | Donor-derived cell-free DNA for detection of acute rejection in lung transplant recipients |
| title_sort | donor derived cell free dna for detection of acute rejection in lung transplant recipients |
| topic | ddcfDNA acute cellular rejection antibody mediated rejection allograft injury lung transplantation non-invasive biomarker |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1531774/full |
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