Cell Free DNA Levels in Patients with Acute Rejection after Lung Transplantation

Abstract

<h3>Purpose</h3> The incidence of acute cellular rejection (ACR) in lung transplant recipients (LTRs) remains about 33% in the first-year post-transplant, the highest for any organ transplant. Although acute rejection frequently responds to treatment, at the present time there is no reliable biomarker to non-invasively monitor response to therapy after ACR treatment . We hypothesized %ddcfDNA levels following acute rejection treatment can predict response to therapy. <h3>Methods</h3> We retrospectively collected clinical and histopathology data on lung transplant recipients treated for ACR who underwent %ddcfDNA testing as part of clinical care between March 2020 and August 2020. <h3>Results</h3> We identified a total of 14 LTRs that were treated for ACR and had a %ddcfDNA value available. One patient had only one %ddcfDNA and was excluded from the analysis. 11/13 patients also had available %ddcfDNA values after treatment. 10/11 of these patients demonstrated a decline in %ddcfDNA level following treatment of rejection(figure 1) The mean reduction in %ddcfDNA after treatment was 55% (Log₁₀ Ratio -0.35; 95% CI, 9% to 78%; p = 0.03). One patient had a significant increase in follow up %ddcfDNA level attributed to persistent ACR and antibody mediated rejection(AMR) requiring Anti-Thymocyte Globuline(ATG) treatment. Subsequent values for this patient also demonstrate that %ddcfDNA levels decrease following aggressive treatment of rejection. One patient(patient 6) had concurrent infection and rejection. <h3>Conclusion</h3> %ddcfDNA may to be a useful biomarker in evaluating allograft post rejection treatment. Persistent high levels are suggestive of ongoing ACR or AMR