Torque Teno Virus Loads as a Marker of Immunosuppression in Pediatric Kidney Transplant Recipients

Background: Long-term
renal function and survival after kidney transplantation rely on appropriate immunosuppressive treatment
to prevent the risk of rejection. New biomarkers are needed to accurately assess the degree of immunosuppression in
renal transplant recipients in order to avoid organ rejection and the development of opportunistic infections. Highly prevalent
in humans, torque teno virus (TTV), which belongs to the family Anelloviridae, is a small, nonenveloped, single-stranded
DNA
virus which has not been linked with any specific human illness, but which constitutes a major component of the human virome.
Host antiviral responses allow TTV levels to be controlled; however, viral persistence remains, explaining the high prevalence in
human populations, including healthy individuals. Important confounders of TTV load include time since transplantation, age,
gender, obesity, and smoking status.
Aims: TTV-based
guidance of immunosuppressive drug dosing could help with risk stratification, reducing the risk of infection,
graft rejection and oncologic disease on an individual level, enabling long-term
patient and graft survival.
Methods: Original studies were accessed by a systematic search from electronic databases including PubMed, ScienceDirect and
Wiley Online Library.
Results: The presented data mainly derive from adult transplant recipients showing an association between TTV plasma levels
and the immune status of the host: High-TTV
load and high immunosuppression are associated with a risk of infection, and low-TTV
load and low immunosuppression indicate a risk of rejection. However, there is minimal information on pediatric transplant
recipients with further research required in this cohort. To date, it has been demonstrated that longer posttransplant times are
significantly associated with lower TTV levels in children with renal transplant. Meanwhile, an association between lower TTV
loads and increased risk of graft reject during the first year of transplantation was also reported. More recently, Eibensteiner et al.
revealed a robust, independent association between TTV plasma load and the onset of Cytomegalovirus and BK virus infections.
Conclusion: Data from randomized controlled trials are still missing, even in adults, but a multicenter randomized controlled
trial for TTV-guided
immunosuppression in adult kidney recipients (TTVguideIT) began in 2022. There is, therefore, great promise
for TTV levels to be used as a biomarker that could potentially improve both graft