Introduction: Torque Teno Virus (TTV) is a small, non-enveloped, single-stranded DNA virus of the Anelloviridae family which has not been linked to any specific human illness but constitutes a major component of the human virome. TTV is ubiquitous and is highly prevalent in humans. Recent studies have shown an association between the TTV plasma viral load and the immune status of the host with reference to viral infection, immunosuppression therapy and acute rejection in transplant recipients. However, there is scant information on pediatric transplant recipients. The aim of our study was to prospectively follow pediatric renal transplant patients and to analyze TTV load before and at different time points after kidney transplantation. In addition, for comparison, we sought to assess TTV viral loads in children who have chronic renal disease and in a cohort of healthy controls.
Methods: Patients attending the Nephrology clinic at Children’s Health Ireland @ Temple Street were recruited for the study. Plasma samples from patients included in the study were pre-transplant (n=10), post-transplant (n=91), chronic renal failure (n=8) and a group of healthy controls (n=23). Following nucleic acid extraction using the MagNA Pure 96 system (Roche, Germany), the TTV viral loads were measured using the TTV R-gene kit (bioMérieux, France). Results are expressed as log10 copies/ml. Statistical analysis was performed using non-parametric Mann-Whitney test for independent samples and p<0.05 was considered statistically significant.
Results: The pre-transplant group, healthy control cohort and chronic renal failure group had similar TTV loads (mean±SE: 2.45±0.5 vs 2.7±0.2 vs 3.2±0.4 log10 copies/ml). TTV loads post-transplant of up to 12 months (5.0±0.3 log10 copies/ml) or beyond a year post-transplant (4.6±0.2 log10 copies/ml) were significantly higher than pre-transplant levels (p<0.002, p<0.001 respectively). Longitudinal monitoring of TTV viral loads in our pediatric renal transplant cohort after transplantation revealed a marked increase in TTV viremia by ≥2 log10 copies/ml from baseline levels. Immunosuppression therapy included tacrolimus, mycophenolate and prednisolone. Target trough levels of tacrolimus levels in these patients ranged from 4-12 ng/ml.
Conclusions: Our findings show that TTV viral load is a promising marker to assess immune competence and associates with immunosuppression in a cohort of pediatric renal transplant recipients. Our findings are in agreement with previous similar reports in adult kidney transplant patients.