Adjunctive Viral Load Assessments of Torque Teno Virus may Enhance Clinical Interpretation of Plasma Donor-derived Cell-free DNA after Lung Transplantation

Abstract: Torque Teno Virus (TTV) viral load (VL) is affected by the net state of immunosuppression after lung transplantation (LT). We speculated TTV VL assessment could complement surveillance with donor-derived cell-free DNA (dd-cfDNA), a validated biomarker for acute rejection (AR). 132 plasma samples were analyzed for both TTV VL and dd-cfDNA%. Median dd-cfDNA% was elevated in biopsy proven AR, chronic lung allograft dysfunction, and infection cohorts (p<0.01, 0.03, 0.10, respectively) compared to stable. TTV loads were significantly lower in patients with higher dd-cfDNA (>1% vs. <1%) in both the <3-month (p=0.013) and >3-month periods (p=0.028). TTV loads were significantly lower in the AR cohort compared with non-AR and stable cohorts in the <3- month timeframe. This data suggests that TTV VL assessment, as an adjunct to routine %dd-cfDNA surveillance after LT, may have utility for distinction of AR, and potentially infection, from stable patients during the initial 3-month period post-LT. If substantiated in multi-center clinical trials, TTV VL may have clinical value as a proxy for net state of immunosuppression and allow for a personalized medicine approach to immunosuppressive drug adaption. Key Words:Torque Teno virus, Anello Virus, cell-free DNA, lung transplantation, acute rejection.