Transplantation Direct (2020-10-01)

Plasma Donor-derived Cell-free DNA Levels Are Increased During Acute Cellular Rejection After Lung Transplant: Pilot Data

  • David Sayah, MD, PhD,
  • S. Samuel Weigt, MD,
  • Allison Ramsey, MD,
  • Abbas Ardehali, MD,
  • Jeff Golden, MD,
  • David J. Ross, MD

DOI
https://doi.org/10.1097/TXD.0000000000001063
Journal volume & issue
Vol. 6, no. 10
p. e608

Abstract

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Background. Telehealth platforms with remote phlebotomy and biomarker implementation represent a novel paradigm for surveillance after lung transplantation (LT). In a pilot study, we investigated donor-derived cell-free DNA (dd-cfDNA) in plasma using a clinical-grade “next-generation sequencing” assay. Methods. dd-cfDNA levels determined in biorepository venous plasma samples obtained during the lung allograft rejection gene expression observation study, implementing a clinical-grade next-generation sequencing assay. Sixty-nine unique LT patients encompassing 9 LT centers, with associated clinical-histopathologic diagnoses, were examined—allograft infection (n = 26), normal histopathology without infection (n = 30), and acute cellular rejection (ACR; n = 13). Results. dd-cfDNA in ACR patients were significantly elevated (1.52%; interquartile range [IQR], 0.520-2.2550) compared with the normal stable patients (0.485%; IQR, 0.220-0.790) (P = 0.026). During allograft infection, dd-cfDNA values were not different (0.595; IQR, 0.270-1.170) from normal (P = 0.282) and ACR (P = 0.100). AUC-receiver operator characteristics curve analysis for allograft ACR was 0.717 (95% confidence interval, 0.547-0.887; P = 0.025). At a 0.87% threshold dd-cfDNA—sensitivity = 73.1%, specificity = 52.9%, positive predictive value = 34.1%, and negative predictive value = 85.5%. Conclusions. dd-cfDNA assessment holds promise as a noninvasive biomarker of “allograft injury” with acute rejection following LT while prospective, multicenter studies should further refine utility across the spectrum of allograft rejection and infection.