Torque teno virus DNA load as a clinical biomarker for immunosuppression and infection risk in early kidney transplantation: a prospective study

Background: Torque teno virus (TTV) load is emerging as a biomarker of net immunosuppression in kidney transplant recipients (KTRs). This study investigated the dynamics of TTV DNA load, its correlations with immune profiles, and its clinical associations during the early posttransplant period. Methods: We prospectively analyzed plasma TTV DNA load in 41 KTRs at baseline, day 7, day 14, and 1 month posttransplant. Lymphocyte subsets (CD3+, CD4+, CD8+, CD19+, and natural killer NK cells) and cytokines (interleukin IL-6, IL-10) were assessed at day 14. Associations among TTV load, immune parameters, and clinical events, including infection and rejection, were examined. Results: TTV load increased significantly from baseline to day 14 (P<0.001) and to 1 month (P<0.001), with a progressive rise beginning at week 2. TTV load consistently exceeded that of healthy controls at all time points (P<0.001 for each comparison). Patients who experienced infections (n=16) had significantly higher TTV loads at days 7 (P=0.006), 14 (P=0.048), and 30 (P=0.044) than patients without infections. At day 14, TTV load showed positive correlations with CD8+ (r=0.677, P<0.001) and CD19+ (r=0.433, P=0.005) cell percentages, as well as with IL-10 levels (r=0.668, P<0.001). Inverse correlations were observed with CD3+ (r=-0.388, P=0.012), CD4+ (r=-0.478, P=0.002), and NK cell percentages (r=-0.340, P=0.030), and with IL-6 levels (r=-0.462, P=0.002). While the percentage of NK cell were significantly higher in patients with infection. Preliminary observations from a very small subset of patients (n=2) suggested that rejection may be associated with lower TTV loads at days 7 and 14; however, this finding requires further investigation. Conclusions: Early posttransplant TTV load reflects the degree of immunosuppression, correlates with specific immune alterations, and predicts infection risk. Monitoring TTV load may provide a valuable tool for personalized immunosuppression management in KTRs.