Torque Teno Virus: A Promising Biomarker in Kidney Transplant Recipients

Abstract

Torque Teno Virus (TTV) is a ubiquitous component of the human virome, not associated with any disease. As its load increases when the immune system is compromised, such as in kidney transplant (KT) recipients, TTV load monitoring has been proposed as a method to assess immunosuppression. In this prospective study, TTV load was measured in plasma and urine samples from 42 KT recipients, immediately before KT and in the first 150 days after it. Data obtained suggest that TTV could be a relevant marker for evaluating immune status and could be used as a guide to predict the onset of infectious complications in the follow-up of KT recipients. Since we observed no differences considering distance from transplantation, while we found a changing trend in days before viral infections, we suggest to consider changes over time in the same subjects, irrespective of time distance from transplantation.

Keywords: Torque Teno Virus; anellovirus; immunosuppression; immunosuppressive therapy; infection; kidney transplantation.

Figure 1

Changes in mean levels of plasma (panel a) and urine (panel b) TTV during follow-up. (Panel c): Change in pTTV by uTTV. Locally weighted regression (PROC SGPLOT with LOESS statement in SAS) using a scatterplot smoothing method that automatically determines the optimal smoothing parameter.

Figure 2

(a) differences between non-infection and infection events. (b) differences between non-infection and cases of CMV infection or reactivation (t test). ns: not significant, * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001.

Figure 3

Distribution of plasma (left) or urine (right) TTV log copies by days from a bacterial (panel a,b) or viral (panel c,d) infection, or CMV reactivations (panel e,f) for subjects with (red) or without (blue) infections. Panel, plasma or urine, infection type and, for infection vs. no infections, total number of subjects, measurements and infection events: (a), plasma, bacterial, 35, 305, 75 vs. 7, 41, 0; (b), urine, bacterial, 35, 268, 66 vs. 7, 35, 0; (c), plasma, viral, 8, 54, 22 vs. 34, 292, 0; (d), urine, viral, 8, 47, 19 vs. 34, 256, 0; (e), plasma, CMV reactivations, 26, 255, 94 vs. 16, 92, 0; (f), urine, CMV reactivations, 26, 22, 86 vs. 16, 81, 0.

Figure 4

Plasma (panel a) or urine (panel b) TTV levels in subjects with a bacterial (blue) or viral (green) infection, or a CMV reactivation (red) during follow-up, according to distance from the day with the infection (day of positivity for infection has been fixed at 0 to align and center the curves); days 0 excluded. Total number of subjects, measurements, and infection events (panel a) plasma TTV levels, bacterial infections (35, 305, 75), viral infections (8, 54, 22), and CMV reactivations (26, 255, 94); (panel b) urine TTV levels, bacterial infections (35, 268, 66), viral infections (18, 47, 19), and CMV reactivations (26, 222, 86).