Plasma Donor-derived Cell-free DNA Levels Are Increased During Acute Cellular Rejection After Lung Transplant: Pilot Data. Issue 10 (October 2020)

• Record Type: Journal Article
• Authors: Sayah, David; Weigt, S. Samuel; Ramsey, Allison; Ardehali, Abbas; Golden, Jeff; Ross, David J.
• Is Part Of: Transplantation direct. Volume 6:Issue 10(2020)
• Publication Date: 2020-10
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation -- Periodicals; 362.19795
• DOI: 10.1097/TXD.0000000000001063
• Languages: English
• ISSNs: 2373-8731

Abstract

Abstract : 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.