Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1531774
This article is part of the Research Topic Antibody-Mediated Rejection After Solid Organ Transplantation View all 8 articles

Donor-derived cell-free DNA for detection of acute rejection in lung transplant recipients

Provisionally accepted
Gökce Yavuz Gökce Yavuz 1*Julia Walter Julia Walter 1Kaimo Hirv Kaimo Hirv 2Oliver Wachter Oliver Wachter 2Andrea Dick Andrea Dick 3Julia Kovács Julia Kovács 1Julia Zimmermann Julia Zimmermann 1Olaf Michael Glueck Olaf Michael Glueck 1Maximilian Vorstandlechner Maximilian Vorstandlechner 1Nicole Samm Nicole Samm 1Jan Michael Fertmann Jan Michael Fertmann 1Wulf Sienel Wulf Sienel 1Sebastian Michel Sebastian Michel 4,5Michael Irlbeck Michael Irlbeck 6Nikolaus Kneidinger Nikolaus Kneidinger 5,7Rudolf Hatz Rudolf Hatz 1,5Jürgen Behr Jürgen Behr 8Christian Schneider Christian Schneider 1,5Teresa Kauke Teresa Kauke 1
  • 1 Division of Thoracic Surgery, LMU Munich University Hospital, Munich, Germany
  • 2 MVZ Martinsried, Martinsried, Germany
  • 3 Division of Transfusion Medicine, LMU Munich University Hospital, Munich, Germany
  • 4 Department of Cardiac Surgery, LMU Munich University Hospital, Munich, Germany
  • 5 German Center for Lung Research (DZL), Comprehensive Pneumology Center (CPC), Munich, Bavaria, Germany
  • 6 Department of Anesthesiology, LMU Munich University Hospital, Munich, Germany
  • 7 Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Styria, Austria
  • 8 Department of Medicine V, LMU Munich University Hospital, Munich, Germany

The final, formatted version of the article will be published soon.

    Acute 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 donorderived cell-free DNA (ddcfDNA) as a non-invasive biomarker for detecting acute rejection in lung transplant recipients (LTR). We 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 (FEV 1 ). Median %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. %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.

    Keywords: ddcfDNA, Acute cellular rejection, Antibody mediated rejection, Allograft injury, Lung Transplantation, Non-invasive biomarker

    Received: 20 Nov 2024; Accepted: 13 Jan 2025.

    Copyright: © 2025 Yavuz, Walter, Hirv, Wachter, Dick, Kovács, Zimmermann, Glueck, Vorstandlechner, Samm, Fertmann, Sienel, Michel, Irlbeck, Kneidinger, Hatz, Behr, Schneider and Kauke. 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) or licensor 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.

    * Correspondence: Gökce Yavuz, Division of Thoracic Surgery, LMU Munich University Hospital, Munich, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.