Using Torque Teno Virus as a Serial Monitoring Tool for the Net State of Immunosuppression of Kidney Transplant Recipients
Study Setup
Design: Post-hoc analysis of longitudinal Torque Teno Virus (TTV) data.
Cohorts:
- Discovery cohort: 252 kidney transplant recipients from the CTOT-08 study (2011–2014), with 1,967 plasma samples and an average of 7.8 visits per patient over 2 years.
- Validation cohort: 162 patients from the Northwestern Biorepository (NWB), with 173 samples.
Sampling: Surveillance biopsies at 2–6-, 12-, and 24-months post-transplant; monthly visits for the first 6 months, then quarterly.
TTV Quantification: Performed using TRACID [metagenomic next-generation sequencing (mNGS)] by Eurofins Transplant Genomics, with validation via qPCR.
Key Findings Enabled by TRACID:
- Longitudinal TTV trajectories (slopes over time) generated via TRACID outperform single-point measurements in predicting subclinical acute rejection (AR) and infection.
- A declining TTV slope combined with low current TTV and high historical TTV average is associated with a 13.88-fold increase in the odds of subclinical AR.
- A rising TTV slope is linked to a 12.15-fold increase in the odds of viral infection.
- TRACID supports a two-threshold framework (logTTV 4.5 and 7.8) to stratify patients into Under-, Even-, and Over-immunosuppression states—enabling personalized IS management.
Immunosuppression (IS) Level Stratification Based on logTTV
| IS Category | logTTV Range | Associated Risk |
| Under-IS | ≤ 4.5 | Increased risk of Subclinical Acute Rejection |
| Even-IS | 4.5 – 7.8 | Baseline Risk (Reference) |
| Over-IS | ≥ 7.8 | Increased risk of Viral Infection over Subclinical AR |
This study validates TRACID’s role in transforming immune monitoring from static snapshots to dynamic, patient-specific insights. It represents a meaningful step toward precision medicine in transplantation, where immunosuppression can be tailored to each patient’s evolving immune status.