Using Torque Teno Virus as a Serial Monitoring Tool for the Net State of Immunosuppression of Kidney Transplant Recipients

Torque Teno Virus (TTV) has emerged as a promising marker reflecting the net state and trajectory of immunosuppression (IS). We analyzed longitudinal TTV data from 252 kidney transplant recipients in a multi-center observational study (average 7.8 visits/patient over 2 years). Patient-specific TTV trajectories, computed as slopes over defined time windows, captured the direction of immune response dynamics. A past 1-year logTTV slope < 0.0066, combined with a low current logTTV (<4.3) and a relatively high historical logTTV average (>5.7), was associated with a 13.88-fold increase in the odds of subclinical AR (95% CI: 5.49-37.42) relative to patients whose slope exceeded 0.0066. In contrast, a past 1-year logTTV slope > 0.076 conferred a 12.15-fold rise in the odds of infection over TX (95% CI: 2.99-81.42). Decision trees incorporating TTV trajectories achieved AUCs of 0.67 for both subclinical AR and infection versus TX-outperforming models using a single TTV measurement. We identified optimal two-sided logTTV thresholds-(4.5,7.8)-stratifying patients into Under-IS, Even-IS, and Over-IS states, where Under-IS status increases subclinical AR odds over TX by 2.39-fold (95% CI: 1.53-3.83), while Over-IS status increases infection odds over subclinical AR by 2.5-fold (95% CI: 1.03-6.42). These findings provide a framework for personalized IS management.