Torque Teno Virus Load Is Associated With Subclinical Alloreactivity in Kidney Transplant Recipients: A Prospective Observational Trial

Transplantation. 2021 Sep 1;105(9):2112-2118. doi: 10.1097/TP.0000000000003619.

Abstract

Background: Nonpathogenic torque teno viruses (TTVs) are highly prevalent in transplant recipients and associated with immunosuppression. Studies in kidney transplant patients have proposed assessment of TTV load for risk stratification of clinically overt graft rejection. The value of TTV quantification in the context of subclinical rejection has not been evaluated.

Methods: In this prospective trial, 307 consecutive kidney transplant recipients were subjected to per-protocol monitoring of plasma TTV. TTV was analyzed in the context of protocol biopsies (n = 82), scheduled 1 year posttransplantation.

Results: TTV load at the time of biopsy was lower in recipients with rejection (n = 19; according to Banff, including borderline changes suspicious for acute T cell-mediated rejection) than those without rejection (n = 63) whereby each log increase in TTV copies/mL decreased the risk for rejection by 9% (risk ratio 0.91, 95% confidence interval, 0.85-0.97; P = 0.004). Development of chronic lesions (cg, cv, ci, ct, ah, ptcml) was associated with the number of days with a TTV load <1 × 106 copies/mL between months 3 and 12 posttransplant (β 0.07, 95% confidence interval, 0.01-0.14; P = 0.02).

Conclusions: This trial demonstrates an association between TTV and subclinical graft rejection in kidney transplant recipients. A TTV load <1 × 106 copies/mL suggests suboptimal immunosuppression.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Virus Infections / diagnosis
  • DNA Virus Infections / immunology
  • DNA Virus Infections / virology*
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • Graft Rejection / virology*
  • Host-Pathogen Interactions
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation* / adverse effects
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Torque teno virus / immunology
  • Torque teno virus / pathogenicity*
  • Treatment Outcome
  • Viral Load*

Substances

  • Immunosuppressive Agents