Torque Teno Virus (TTV) and Epstein–Barr Virus (EBV) Viral Load in Peripheral Blood as a Biomarker of “Net Immunosuppression”: Factors Influencing Viral Load in Adult Patients Awaiting Solid Organ Transplantation

Abstract

BackgroundQuantitative measurement of DNA levels of persistent highly prevalent viral infections such as Torque Teno Virus (TTV) and Epstein–Barr Virus (EBV) that are highly dependent on T-cell responses for control have been proposed as possible biomarkers of “net immunosuppression.”MethodsWe examined factors influencing TTV in 51 adult patients awaiting solid organ transplantation (15 kidney, 15 liver/small bowel, 10 heart, 11 lung) and 51 healthy age- and sex-matched controls. Samples from all patients were tested for TTV DNA (plasma) using quantitative nucleic acid testing (QNAT), EBV and cytomegalovirus (CMV) serology, CMV DNA (QNAT of plasma, urine, saliva), and EBV DNA (QNAT of whole blood [WB], saliva). Effects of age, sex, organ, CMV serology, and EBV DNA on TTV DNA were explored in univariate and multivariate models.ResultsPatients and controls were well-matched for age (median 48.4 vs. 49.2 years), sex 64.7% M, both CMV seropositivity (45.1% vs. 51%) and EBV seropositivity (94.1% vs. 98.0%), and detection of EBV DNA in saliva (52.9% vs. 50.0%) and WB (28.6% vs. 16.3%). TTV DNA was detected more frequently and at higher levels (Figure 1) in patients (86.3%) vs. controls (66.7%). TTV DNA plasma levels were age-dependent for patients but not controls (<50 years vs. >50 years, P = 0.021), and were only higher in patients >50 years vs. controls (P = 0.003). Only two patients and no controls had CMV DNA detected. Neither CMV serostatus nor sex impacted TTV DNA levels in patients or controls. Patients awaiting lung transplant had lower TTV levels compared with those awaiting liver (P = 0.04) or heart transplant (P = 0.03). A significant correlation between plasma TTV DNA levels and WB EBV DNA (r = 0.28, P = 0.05) but not saliva EBV DNA levels was observed in patients (Figure 2); only WB EBV DNA level was a significant predictor of high (≥3rd quartile of control) TTV DNA levels in patients in multivariate analysis (P = 0.026). Four of the five patients tested before and 27–285 days after transplant had a significant post-transplant rise in TTV DNA levels (Figure 3).ConclusionMeasurement of TTV DNA in plasma alone or combined with EBV DNA in WB may be a useful marker for measuring global immunosuppression including age-related immunosenescence in subjects not receiving exogenous immunosuppression.Disclosures All authors: No reported disclosures.