Torque teno virus loads after kidney transplantation predict allograft rejection but not viral infection

https://doi.org/10.1016/j.jcv.2021.104871Get rights and content
Under a Creative Commons license
open access

Highlights

  • TTV loads increase substantially with immunosuppression after kidney transplantation.

  • With every 10-fold TTV load-increase the risk of organ rejection decreases with 25%.

  • With every TTV load-increase, the risk of BKV and CMV infection stays the same.

  • TTV load can be used as a predictive marker of rejection after transplantation.

  • TTV load values could guide individual immunosuppressive drug dosing.

Abstract

The main challenge of immunosuppressive therapy after solid organ transplantation is to create a new immunological balance that prevents organ rejection and does not promote opportunistic infection. Torque teno virus (TTV), a ubiquitous and non-pathogenic single-stranded DNA virus, has been proposed as a marker of functional immunity in immunocompromised patients. Here we investigate whether TTV loads predict the risk of common viral infection and allograft rejection in kidney transplantation recipients.

In a retrospective cohort of 389 kidney transplantation recipients, individual TTV loads in were measured by qPCR in consecutive plasma samples during one year follow-up. The endpoints were allograft rejection, BK polyomavirus (BKPyV) viremia and cytomegalovirus (CMV) viremia. Repeated TTV measurements and rejection and infection survival data were analysed in a joint model.

During follow-up, TTV DNA detection in the transplant recipients increased from 85 to 100%. The median viral load increased to 107 genome copies/ml within three months after transplantation. Rejection, BKPyV viremia and CMV viremia occurred in 23%, 27% and 17% of the patients, respectively. With every 10-fold TTV load-increase, the risk of rejection decreased considerably (HR: 0.74, CI 95%: 0.71–0.76), while the risk of BKPyV and CMV viremia remained the same (HR: 1.03, CI 95%: 1.03–1.04 and HR: 1.01, CI 95%: 1.01–1.01).

In conclusion, TTV load kinetics predict allograft rejection in kidney transplantation recipients, but not the BKPyV and CMV infection. The potential use of TTV load levels as a guide for optimal immunosuppressive drug dosage to prevent allograft rejection deserves further validation.

Keywords

TTV
Anellovirus
BK virus infection
CMV infection
Biomarker of immunity in KTx
Immunocompromised

Cited by (0)

1

Current address: Department of Medical Microbiology, University Medical Center Utrecht, the Netherlands