Abstract

Introduction

Donor-derived cell-free DNA has been validated in recipients of single organ transplants, either heart or lung. We looked into the clinical utility of detecting acute rejection in recipients of combined heart-lung transplants using a novel PCR-based assay that measures absolute dd-cfDNA levels.

Material and Methods

To analyse donor-derived cell-free DNA using a real-time PCR-based test, serum samples were collected concurrently with transbronchial and endomyocardial biopsies from 30 recipients of simultaneous heart-lung transplant recipients. Regression analyses were done to assess how donor-derived cell-free DNA levels were affected by the recipient and donor-derived characteristics.

Results

The patients had a mean age of 38.87 years (range: 18-72 years), 60% of whom were male, and a BMI of 21.62. (range: 17.4- 27.2). Cyanosis of the heart was the most typical pre-transplant diagnosis (n=11, 36.7%). In comparison to healthy allografts (median 7.25 ng/l, interquartile range (IQR):-0.0- 43.3 ng/l), heart or lung allograft injuries had considerably higher absolute dd-cfDNA levels (median 37.0 ng/l, IQR:-12.5- 94.35 ng/l). With a 10 ng/mL threshold, the sensitivity and specificity were 63.6% and 66.7%, respectively, with positive and negative predictive values of 33.3% and 88.9%. The investigated metrics did not reach statistical significance for dd-cfDNA levels.

Conclusion

The plasma levels of dd-cfDNA may be a less invasive technique to predict acute allograft injury even in combined heart-lung transplant recipients. Further studies are investigating organ-specific donor-derived cell-free RNA levels(heart-cfRNA & lung-cfRNA) to delineate organ injury.