AUTHOR=Noda Kentaro , Snyder Mark E. , Xu Qingyong , Peters David , McDyer John F. , Zeevi Adriana , Sanchez Pablo G. TITLE=Single center study investigating the clinical association of donor-derived cell-free DNA with acute outcomes in lung transplantation JOURNAL=Frontiers in Transplantation VOLUME=2 YEAR=2024 URL=https://www.frontiersin.org/journals/transplantation/articles/10.3389/frtra.2023.1339814 DOI=10.3389/frtra.2023.1339814 ISSN=2813-2440 ABSTRACT=Background

Circulating donor-derived cell-free DNA (dd-cfDNA) levels have been proposed as a potential tool for the diagnosis of graft injury. In this study, we prospectively investigated dd-cfDNA plasma levels and their association with severe primary graft dysfunction (PGD) and graft rejection after lung transplant.

Methods

A total of 40 subjects undergoing de-novo lung transplants at our institution were recruited in this study. Blood samples were collected at various time points before and after lung transplant for 1 year. Dd-cfDNA in samples was determined using AlloSure assay (CareDx Inc.). The correlation of the value of %dd-cfDNA was investigated with the incidence of PGD, acute cellular rejection (ACR), and donor-specific antibody.

Results

We observed a rapid increase of %dd-cfDNA in the blood of recipients after lung transplantation compared to baseline. The levels of dd-cfDNA decreased during the first two weeks. The peak was observed within 72 h after transplantation. The peak values of %dd-cfDNA varied among subjects and did not correlate with severe PGD incidence. We observed an association between levels of %dd-cfDNA from blood collected at the time of transbronchial biopsy and the histological diagnosis of ACR at 3 weeks.

Conclusion

Our data show that circulating dd-cfDNA levels are associated with ACR early after transplantation but not with severe PGD. Plasma levels of dd-cfDNA may be a less invasive tool to estimate graft rejection after lung transplantation however larger studies are still necessary to better identify thresholds.