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

ABSTRACT: 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.

SUBMITTER: Sayah D 

PROVIDER: S-EPMC7515612 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature