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.
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References
International Committee on Taxonomy of Viruses (2018) ICTV. https://talk.ictvonline.org
Focosi D, Antonelli G, Pistello M, Maggi F (2016) Torquetenovirus: the human virome from bench to bedside. Clin Microbiol Infect 22:589–593
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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).
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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
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DOI: https://doi.org/10.1007/s00430-019-00586-w