Quantification of torque teno virus (TTV) DNA in saliva and plasma samples in patients at short time before and after kidney transplantation

Quantification of torque teno virus (TTV) DNA in saliva and plasma samples in patients at short time before and after kidney transplantation

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Introduction

Increasing evidence has suggested that measuring the torque teno virus (TTV) load after immunosuppressive treatment may be a useful tool to evaluate the efficacy of immunosuppression. TTV is a naked, small virus with a circular single-strand DNA genome, discovered in 1997 , comprising to date at least 29 genetically different species included in the genus Alphatorquevirus within the Anelloviridae family.

TTV possesses several characteristics, such as its presence as a main virus of the human virome, high viral load in immunosuppressed patients compared to healthy ones, considerable genetic diversity, and lack of association with any human illness. Several studies have investigated the viral load and kinetics of TTV in human plasma by associating the former with immune status, presence of infection, and organ rejection after transplantation.

To date, although T cells are considered to be the main site of TTV replication , other cell types may allow viral replication. Therefore, saliva has gained increased interest as a non-invasive screening approach to assess the TTV DNA viral load. TTV DNA has been recently investigated in the saliva and compared with paired plasma samples obtained during allogeneic hematopoietic stem cell transplantation.

Aim

To investigate the correlation between the TTV viral load and immune function in paired saliva and plasma samples in patients on kidney transplantation.

Materials and Methods

Clinical and demographic characteristics of the patients were collected during an interview. Only patients with renal transplant were included. The samples (saliva and blood) were collected in three different experimental periods as follows: the first within 24 hours before renal transplantation, the second between 15 and 20 days and the third between 45 and 60 days after the surgery.

Blood samples were collected by nurses at the same moment of the saliva collection. After collection and identification, the samples were centrifuged at 800 rpm in a conical tube and then 200 μL of each sample were aliquoted into cryotubes for storage in a freezer at − 80°C. TTV-DNA viral load was quantified in paired samples of saliva and plasma from 71 patients before and a short-time after renal-transplantation by real-time PCR.

Results

The data obtained from 213 paired samples showed a slight consistency in the comparison between saliva and plasma, with prevalence of TTV-DNA being 58%, 52% and 60% in saliva samples and 60%, 73% and 90% in plasma samples before and at 15–20 and 45–60 days after transplantation, respectively. Additionally, a high TTV viral load was observed in plasma at 15–20 and 45–60 days after transplantation compared to that observed in saliva at the same time.

In all TTV positive patients, the viral load showed a skewed distribution (Kolmogorov-Smirnov test, P < 0.001). Additionally, Spearman’s correlation test (coefficient = 0.323; P < 0.001) showed a weak positive correlation between the viral load of TTV found in saliva and plasma (Figure 1).

Conclusion

Overall, monitoring TTV-DNA in saliva samples could be an additional fast non-invasive option to assess the immune functionality in SOT populations.

References

  1. Cozzi E, Colpo A, De Silvestro G. The mechanisms of rejection in solid organ transplantation. Transfus Apher Sci. 2017;56(4):498–8.
  2. Sánchez-Fueyo A, Strom TB. Immunologic basis of graft rejection and tolerance following transplantation of liver or other solid organs. Gastroenterology. 2011;140(1):51–64.
  3. Rezahosseini O, Drabe CH, Sørensen SS, et al. Torque-Teno virus viral load as a potential endogenous marker of immune function in solid organ transplantation. Transplantation Reviews. 2019;33(3):137–144.
  4. Focosi D, Maggi F, Albani M, et al. Torquetenovirus viremia kinetics after autologous stem cell transplantation are predictable and may serve as a surrogate marker of functional immune reconstitution. J Clin Virol. 2010;47(2):189–192.
  5. Nishizawa T, Okamoto H, Konishi K, et al. A novel DNA virus (TTV) associated with elevated transaminase levels in post-transfusion hepatitis of unknown etiology. Biochem Biophys Res Commun. 1997;241(1):92–97.
  6. Okamoto H. History of discoveries and pathogenicity of TT viruses. Curr Top Microbiol Immunol. 2009;331:1–20.
  7. Spandole S, Cimponeriu D, Berca LM, et al. Human anelloviruses: an update of molecular, epidemiological and clinical aspects. Arch Virol. 2015;160(4):893‐908.
  8. Bendinelli M, Pistello M, Maggi F, et al. Molecular properties, biology, and clinical implications of TT virus, a recently identified widespread infectious agent of humans. Clin Microbiol Rev. 2001;14(1):98‐113.
  9. Kaczorowska J. van der Hoek L. Human anelloviruses: diverse, omnipresent and commensal members of the virome. FEMS Microbiol Rev. 2020;44(3):305–313.
  10. Virgin HW, Wherry EJ, Ahmed R. Redefining chronic viral infection. Cell. 2009;138(1):30–50.
  11. Focosi D, Antonelli G, Pistello M, et al. Torquetenovirus: the human virome from bench to bedside. Clin Microbiol Infect. 2016;22(7):589–593.
  12. Focosi D, Macera L, Pistello M, et al. Torque Teno virus viremia correlates with intensity of maintenance immunosuppression in adult orthotopic liver transplant. J Infect Dis. 2014;210(4):667–668.
  13. Beland K, Dore-Nguyen M, Gagne MJ, et al. Torque Teno virus in children who underwent orthotopic liver transplantation: new insights about a common pathogen. J Infect Dis. 2014;209(2):247–254.
  14. Schiemann M, Puchhammer-Stockl E, Eskandary F, et al. Torque Teno virus load-inverse association with antibody-mediated rejection after kidney transplantation. Transplantation. 2017;101(2):360–367.
  15. Simonetta F, Pradier A, Masouridi-Levrat S, et al., Swiss Transplant Cohort Study (STCS). Torque Teno virus load and acute rejection after orthotopic liver transplantation. Transplantation. 2017;101(7):e219–221.
  16. Abbas AA, Diamond JM, Chehoud C, et al. The perioperative lung transplant Virome: torque Teno viruses are elevated in donor lungs and show divergent dynamics in primary graft dysfunction. Am J Transplant. 2017;17(5):1313–1324.
  17. Nordén R, Magnusson J, and Lundin A, et al. Quantification of torque teno virus and Epstein-Barr virus is of limited value for predicting the net state of immunosuppression after lung transplantation. Open Forum Infect Dis. 2018;5(4) ;ofy050. doi:https://doi.org/10.1093/ofid/ofy50.
  18. Ruiz P, Martínez-Picola M, Santana M, et al. Torque teno virus is associated with the state of immune suppression early after liver transplantation. Liver Transpl. 2019;25(2):302‐310.
  19. Görzer I, Jaksch P, Kundi M, et al. Pretransplant plasma torque teno virus load and increase dynamics after lung transplantation. PLoS One. 2015;10(4):e0122975.
  20. Frye BC, Bierbaum S, Falcone V, et al. Kinetics of torque teno virus‐ DNA plasma load predict rejection in lung transplant recipients. Transplantation. 2019;103(4):815–822.
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