Skip to main content

Advertisement

Log in

Kinetics of Alphatorquevirus plasma DNAemia at late times after allogeneic hematopoietic stem cell transplantation

  • Original Investigation
  • Published:
Medical Microbiology and Immunology Aims and scope Submit manuscript

Abstract

Torque teno virus (TTV) plasma DNA load has been consistently shown to be a surrogate biomarker of immunosuppression in solid organ transplant recipients. It is uncertain whether it may behave similarly in allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). Here, we characterized the dynamics of TTV DNAemia in patients undergoing T-cell replete allo-SCT at late times after transplantation (> day + 100). This retrospective single-center observational study included 33 allo-HSCT patients. Plasma TTV DNA loads were quantified by real-time PCR before initiating the conditioning regimen and at different time points after transplant. Absolute lymphocyte counts (ALC) were measured by flow cytometry. Overall, TTV DNA load increased steadily after engraftment, reaching a peak by day + 90; afterwards, it remained relatively constant until day + 210. TTV DNA loads measured within days + 120 and + 210 correlated inversely with paired ALC, while both parameters did correlate directly within days + 20 and + 60. The median TTV DNA area under a curve between days + 90 and + 210 [(AUC)90–210] was significantly higher in patients who received corticosteroids within this time frame for treatment of graft versus host disease (either acute, chronic or both) than in controls (P = 0.025). In summary, TTV DNA load may mirror the degree of immunosuppression at late times after allo-HSCT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. International Committee on Taxonomy of Viruses (2018) ICTV. https://talk.ictvonline.org

  2. Focosi D, Antonelli G, Pistello M, Maggi F (2016) Torquetenovirus: the human virome from bench to bedside. Clin Microbiol Infect 22:589–593

    Article  CAS  PubMed  Google Scholar 

  3. De Vlaminck I, Khush KK, Strehl C, Kohli B, Luikart H, Neff NF, Okamoto J, Snyder TM, Cornfield DN, Nicolls MR, Weill D, Bernstein D, Valantine HA, Quake SR (2013) Temporal response of the human virome to immunosuppression and antiviral therapy. Cell 155:1178–1187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gorzer I, Jaksch P, Kundi M, Seitz T, Klepetko W, Puchhammer-Stockl E (2015) Pre-transplant plasma Torque Teno virus load and increase dynamics after lung transplantation. PLoS One 10:e0122975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Beland K, Dore-Nguyen M, Gagne MJ, Patey N, Brassard J, Alvarez F, Halac U (2014) Torque Teno Virus in children who underwent orthotopic liver transplantation: new insights about a common pathogen. J Infect Dis 209:247–254

    Article  CAS  PubMed  Google Scholar 

  6. Focosi D, Macera L, Pistello M, Maggi F (2014) Torquetenovirus (TTV) viremia correlates with intensity of maintenance immunosuppression in adult orthotopic liver transplantation. J Infect Dis 210:667–668

    Article  PubMed  Google Scholar 

  7. Gorzer I, Haloschan M, Jaksch P, Klepetko W, Puchhammer-Stockl E (2014) Plasma DNA levels of Torque teno virus and immunosuppression after lung transplantation. J Heart Lung Transpl 33:320–328

    Article  Google Scholar 

  8. Schiemann M, Puchhammer-Stöckl E, Eskandary F, Kohlbeck P, Rasoul- Rockenschaub S, Heilos A, Kozakowski N, Görzer I, Kikić Ž, Herkner H, Böhmig GA, Bond G (2017) Torque teno virus load-inverse association with antibody-mediated rejection after kidney transplantation. Transplantation 101:360–367

    Article  PubMed  PubMed Central  Google Scholar 

  9. Simonetta F, Pradier A, Masouridi-Levrat S, van Delden C, Giostra E, Morard I, Mueller N, Muellhaupt B, Valli PV, Semmo N, Seebach J, Chalandon Y, Kaiser L, Roosnek E (2017) Torque teno virus load and acute rejection after orthotopic liver transplantation. Transplantation 101:e219–e221

    Article  PubMed  Google Scholar 

  10. Jaksch P, Kundi M, Görzer I, Muraközy G, Lambers C, Benazzo A, Hoetzenecker K, Klepetko W, Puchhammer-Stöckl E (2018) Torque teno virus as a novel biomarker targeting the efficacy of immunosuppression after lung transplantation. J Infect Dis 218:1922–1928

    Article  PubMed  Google Scholar 

  11. Kanda Y, Tanaka Y, Kami M, Saito T, Asai T, Izutsu K, Yuji K, Ogawa S, Honda H, Mitani K, Chiba S, Yazaki Y, Hirai H (1999) TT virus in bone marrow transplant recipients. Blood 93:2485–2490

    CAS  PubMed  Google Scholar 

  12. Maggi F, Focosi D, Albani M, Lanini L, Vatteroni ML, Petrini M, Ceccherini- Nelli L, Pistello M, Bendinelli M (2010) Role of hematopoietic cells in the maintenance of chronic human torquetenovirus plasma viremia. J Virol 84:6891–6893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Masouridi-Levrat S, Pradier A, Simonetta F, Kaiser L, Chalandon Y, Roosnek E (2016) Torque teno virus in patients undergoing allogeneic hematopoietic stem cell transplantation for hematological malignancies. Bone Marrow Transpl 51:440–442

    Article  CAS  Google Scholar 

  14. Albert E, Solano C, Pascual T, Torres I, Macera L, Focosi D, Maggi F, Giménez E, Amat P, Navarro D (2017) Dynamics of torque teno virus plasma DNAemia in allogeneic stem cell transplant recipients. J Clin Virol 94:22–28

    Article  CAS  PubMed  Google Scholar 

  15. Albert E, Solano C, Giménez E, Focosi D, Pérez A, Macera L, Piñana JL, Boluda JCH, Maggi F, Navarro D (2018) The kinetics of torque teno virus plasma DNA load shortly after engraftment predicts the risk of high-level CMV DNAemia in allogeneic hematopoietic stem cell transplant recipients. Bone Marrow Transpl 53:180–187

    Article  CAS  Google Scholar 

  16. Gilles R, Herling M, Holtick U, Heger E, Awerkiew S, Fish I, Höller K, Sierra S, Knops E, Kaiser R, Scheid C, Di Cristanziano V (2017) Dynamics of Torque Teno virus viremia could predict risk of complications after allogeneic hematopoietic stem cell transplantation. Med Microbiol Immunol 206:355–362

    Article  CAS  PubMed  Google Scholar 

  17. Wohlfarth P, Leiner M, Schoergenhofer C, Hopfinger G, Goerzer I, Puchhammer-Stoeckl E, Rabitsch W (2018) Torquetenovirus dynamics and immune marker properties in patients following allogeneic hematopoietic stem cell transplantation: a prospective longitudinal study. Biol Blood Marrow Transpl 24:194–199

    Article  Google Scholar 

  18. Fauci AS (1975) Mechanisms of corticosteroid action on lymphocyte subpopulations. I. Redistribution of circulating T and b lymphocytes to the bone marrow. Immunology 28:669–680

    Google Scholar 

  19. Albert E, Torres I, Talaya A, Giménez E, Piñana JL, Hernández-Boluda JC, Focosi D, Macera L, Maggi F, Solano C, Navarro D (2018) Kinetics of torque teno virus DNA load in saliva and plasma following allogeneic hematopoietic stem cell transplantation. J Med Virol 90:1438–1443

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank Juan Manuel Moya Serrano for his technical assistance. Estela Giménez holds a Río-Hortega Contract from the Carlos III Health Institute (ISCIII) (Ref. CM16/00200). Eva María Mateo is grateful to Ministry of Economy and Competitiveness (MINECO, Spanish Government) for a postdoctoral contract “Juan de la Cierva” (Ref. FJCI-2015-25992).

Funding

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David Navarro.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Edited by: Matthias J. Reddehase.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 49 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Albert, E., Solano, C., Giménez, E. et al. Kinetics of Alphatorquevirus plasma DNAemia at late times after allogeneic hematopoietic stem cell transplantation. Med Microbiol Immunol 208, 253–258 (2019). https://doi.org/10.1007/s00430-019-00586-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00430-019-00586-w

Keywords

Navigation