Early Phase Circulating Donor-Derived Cell-Free DNA in Patients after Lung Transplantation

Abstract

<h3>Purpose</h3> Detection of donor-derived cell-free DNA (dd-cfDNA) in circulating blood of posttransplant recipients is a clinically informative tool to predict acute allograft injury and rejection, although its reliability and feasibility have not been extensively studied in lung transplantation. Here, we present our preliminary data of dd-cfDNA in lung transplant patients during the early posttransplant phase. <h3>Methods</h3> Eight subjects were included in this study among patients received double lung transplants at our institute between Jun.-Sept. 2020. Re-transplantation cases were excluded per the study protocol. Blood samples were collected at various times from these consented patients before and after transplantation. Dd-cfDNA in obtained blood samples were determined using AlloSure dd-cfDNA test kits (CareDx, Inc). <h3>Results</h3> Of the 8 subjects, none developed severe primary graft dysfunction and two patients presented acute cellular rejection (ACR) after lung transplantation. All subjects exhibited increased dd-cfDNA immediately after transplantation with a peak percentage of dd-cfDNA (range 12-27%) within 48h posttransplant. (Figure 1). Over 2 weeks, dd-cfDNA percentage declined with significant variation reaching a similar level of <5%, although patients with severe systemic conditions displayed an overall lower percentage of circulating dd-cfDNA versus recipient derived cfDNA. One patient with early ACR and early spike in donor specific antibodies (DSA) showed a relative slower decline in dd-cfDNA than the ACR alone case. <h3>Conclusion</h3> To our knowledge, this is the first report of acute time-dependent changes of dd-cfDNA in patients immediately after lung transplantation. Our preliminary data suggest that recipients' systemic condition may mask the appearance of dd-cfDNA. Additional information regarding circulating whole cfDNA in patients may assist in more accurate detection of dd-cfDNA in the acute phase.