TTV R-GENE®

Real-time PCR assay for Torque Teno Virus detection and quantification to support transplant management

  • TTV viral load monitoring can be used to evaluate the immune status of adult transplant patients and is an aid to assess the immune function
  • TTV monitoring could help optimize immunosuppressive drugs reducing the risk for infections and rejection
  • Part of the EU funded project (TTV GUIDE TX) aims to demonstrate the safety and preliminary efficacy of TTV-guided dosing of immunosuppressive drugs in kidney transplant recipients.

Torque Teno Virus (TTV): a surrogate marker of immune function

Graft rejection due to inadequate immunosuppression is the leading cause for chronic graft dysfunction and infectious disease due to reduced immune function is a major cause of death. Optimization of immunosuppressive drugs is a crucial step to minimize the risk of infection and rejection and thereby prolonging patient and graft survival.

The Torque Teno Virus (TTV) is a non-pathogenic virus carried by nearly everyone and interestingly, research has demonstrated TTV peripheral blood copy number is associated with the grade of the immunosuppression of the host (1,2,3). If the immune system is strong, the TT virus load is low; this indicates a risk for graft rejection (6,8). If the immune system is weak, the TT virus load is high; this indicates a risk of opportunistic infections (4, 10,16).

The quantification of the TT virus load in the blood of transplant recipients might help optimize immunosuppressive drugs and thus reduce risk for infections and rejection.

European Project on Kidney Transplant

A EU funded project - TTV GUIDE TX - aims to demonstrate the safety and preliminary efficacy of TTV-guided dosing of immunosuppressive drugs in kidney transplant recipients. TTV allows for a comprehensive and personalized assessment of the function of the immune system. For the first time, this novel and original approach will be tested in an interventional, randomized and controlled clinical trial including hundreds of kidney transplant recipients from all over Europe.

Coordinated by the Medical University of Vienna (Austria), the TTV GUIDE TX brings together 19 partners from 7 EU countries, including kidney transplant physicians, clinical virologists, project and clinical trial managers, ethicists and bioMérieux, to run a clinical trial with almost 300 patients.

The TTV GUIDE TX project will work closely together with The European Kidney Patients’ Federation (EKPF), the European umbrella organization for 23 national kidney patients’ associations. Once established in routine clinical care, TT virus guidance might reduce thousands of infections and kidney transplant rejections each year.

In the future the TT virus might not only help kidney transplant recipients but also patients with liver, heart and lung transplantation and guide therapy in autoimmune, infectious and oncologic diseases

Find out more about the project at: https://www.ttv-guide.eu/

Please go to: https://vimeo.com/545093421 to see the project video.

List of partners :

TTV R-GENE® kit: a promising biomarker for tailored transplant patients management

The TTV R‑GENE® kit, using the real‑time PCR technology after extraction of the viral DNA, enables the detection and quantification the genome of TTV in whole blood and plasma samples. Results are available in 75 minutes (extraction step not included).

Combined with other biological investigation methods (medical imaging, white blood cell count, lymphocyte phenotyping, etc.), the results obtained with the TTV R‑GENE® kit enable TTV viral load monitoring and are an aid to assess the immune function: TTV viral load monitoring can be used to evaluate the immune status of adult transplant patients.

This kit is intended for in vitro diagnostic use only, in clinical laboratories by laboratory health professionals

TTV R-GENE® (423 414)
Principle of the test Genomic detection and quantification of TTV
Ordering information Reference 423 414 – TTV R-GENE® - Real-Time Detection and Quantification kit
Technology Real-Time PCR / 5‘ nuclease Taqman technology
Gene target TTV 5'-UTR region
Specimen Whole blood, Plasma
Detection limit 250 copies/mL
Dynamic Range of Quantification From 250 to 10^9 copies/mL
Controls included Extraction + Inhibition control, Sensitivity control, Negative control
Results within 75 minutes (extraction step not included)
Reporting unit Copies/mL
Number of tests 90 tests
Storage conditions -15°C/-31°C
Validated Extraction platform
  • EMAG®
  • NUCLISENS® easyMAG®
  • MagNA Pure 96
  • QIAsymphony SP
Validated Amplification platform
  • ABI 7500 Fast, ABI 7500 Fast Dx
  • LightCycler 480 (System II)
  • QuantStudio 5, QuantStudio 5 Dx
  • CFX96
  • Rotor-Gene Q
Status For in vitro diagnostic use

 

  1. Doberer K, Schiemann M, Strassl R, Haupenthal F, Dermuth F, Görzer I, Eskandary F, Reindl-Schwaighofer R, KikićŽ, Puchhammer-Stöckl E, Böhmig GA, Bond G. Torque teno virus for risk stratification of graft rejection and infection in kidney transplant recipients-A prospective observational trial. Am J Transplant. 2020 Aug;20(8):2081-2090. doi:10.1111/ajt.15810. Epub 2020 Mar 8. https://pubmed.ncbi.nlm.nih.gov/32034850/

  2. Pradier A, Masouridi-Levrat S, Bosshard C, Dantin C, Vu DL, Zanella MC, Boely E, Tapparel C, Kaiser L, Chalandon Y, Simonetta F, Roosnek E. Torque Teno Virus as a Potential Biomarker for Complications and Survival After Allogeneic Hematopoietic Stem Cell Transplantation. Front Immunol. 2020 May 27;11:998. doi: 10.3389/fimmu.2020.00998. eCollection 2020. https://pubmed.ncbi.nlm.nih.gov/32536920/

  3. Focosi D, Spezia PG, Macera L, Salvadori S, Navarro D, Lanza M, Antonelli G, Pistello M, Maggi F. Assessment of prevalence and load of torquetenovirus viraemia in a large cohort of healthy blood donors. Clin Microbiol Infect. 2020 Jan 20:S1198-743X(20)30036-7. doi: 10.1016/j.cmi.2020.01.011. https://pubmed.ncbi.nlm.nih.gov/31972321/

  4. Gore EJ, Gomes-Neto AW, Wang L, Bakker SJL, Niesters HGM, de Joode AAE, Verschuuren EAM, Westra J, Leer- Buter CV. Torquetenovirus Serum Load and Long-Term Outcomes in Renal Transplant Recipients. J Clin Med. 2020 Feb 6;9(2):440. doi: 10.3390/jcm9020440. https://pubmed.ncbi.nlm.nih.gov/32041187/

  5. Peker BO, Daloğlu AE, Görzer I, Puchhammer-Stöckl E, Parkan ÖM, Akbaş H, Kintrup GT, Mutlu D, Küpesiz OA, Çolak D. Investigation of Torque Teno Virus (TTV) DNA as an immunological and virological marker in pediatric hematopoietic stem cell transplantation (HSCT) patients. Microb Pathog. 2020 Jul 21;149:104397. doi: 10.1016/ j.micpath.2020.104397. https://pubmed.ncbi.nlm.nih.gov/32707315/

  6. Rezahosseini O, Drabe CH, Sørensen SS, Rasmussen A, Perch M, Ostrowski SR, Nielsen SD. Torque-Teno virus viral load as a potential endogenous marker of immune function in solid organ transplantation. Transplant Rev (Orlando). 2019 Jul;33(3):137-144. https://pubmed.ncbi.nlm.nih.gov/30981537/

  7. Solis M, Velay A, Gantner P, Bausson J, Filipputtu A, Freitag R, Moulin B, Caillard S, Fafi-Kremer S. Torquetenovirus viremia for early prediction of graft rejection after kidney transplantation. J Infect. 2019 Jul;79(1):56-60. https://pubmed.ncbi.nlm.nih.gov/31100359/ Strassl R, Doberer K, Rasoul-Rockenschaub S, Herkner H, Görzer I, Kläger JP, Schmidt R, Haslacher H, Schiemann

  8. Strassl R, Doberer K, Rasoul-Rockenschaub S, Herkner H, Görzer I, Kläger JP, Schmidt R, Haslacher H, Schiemann M, Eskandary FA, Kikić Ž, Reindl-Schwaighofer R, Puchhammer-Stöckl E, Böhmig GA, Bond G. Torque Teno Virus for Risk Stratification of Acute Biopsy-Proven Alloreactivity in Kidney Transplant Recipients. J Infect Dis. 2019 May 24;219(12):1934-1939. https://pubmed.ncbi.nlm.nih.gov/30668796/

  9. Focosi D, Maggi F. Torque teno virus monitoring in transplantation: The quest for standardization. Am J Transplant. 2019 May;19(5):1599-1601. https://pubmed.ncbi.nlm.nih.gov/30468687/

  10. Fernández-Ruiz M, Albert E, Giménez E, Ruiz-Merlo T, Parra P, López-Medrano F, San Juan R, Polanco N, Andrés A, Navarro D, Aguado JM. Monitoring of alphatorquevirus DNA levels for the prediction of immunosuppression-related complications after kidney transplantation. Am J Transplant. 2019 Apr;19(4):1139-1149. https://pubmed.ncbi.nlm.nih.gov/30346659/

  11. Albert E, Solano C, Giménez E, Focosi D, Pérez A, Macera L, Piñana JL, Mateo EM, Boluda JCH, Maggi F, Navarro D. Kinetics of Alphatorquevirus plasma DNAemia at late times after allogeneic hematopoietic stem cell transplantation. Med Microbiol Immunol. 2019 Apr;208(2):253-258. https://pubmed.ncbi.nlm.nih.gov/30852649/

  12. Frye BC, Bierbaum S, Falcone V, Köhler TC, Gasplmayr M, Hettich I, Dürk T, Idzko M, Zissel G, Hengel H, Müller- Quernheim J. Kinetics of Torque Teno Virus-DNA Plasma Load Predict Rejection in Lung Transplant Recipients. Transplantation. 2019 Apr;103(4):815-822 https://pubmed.ncbi.nlm.nih.gov/30234787/

  13. Macera L, Spezia PG, Medici C, Rofi E, Del Re M, Focosi D, Mazzetti P, Navarro D, Antonelli G, Danesi R, Pistello M, Maggi F. Comparative evaluation of molecular methods for the quantitative measure of torquetenovirus viremia, the new surrogate marker of immune competence. J Med Virol. 2019 Apr 19. https://pubmed.ncbi.nlm.nih.gov/31002743/

  14. Ruiz P, Martínez-Picola M, Santana M, Muñoz J, Pérez-Del-Pulgar S, Koutsoudakis G, Sastre L, Colmenero J, Crespo G, Navasa M. Torque Teno Virus Is Associated With the State of Immune Suppression Early After Liver Transplantation. Liver Transpl. 2019 Feb;25(2):302-310. https://pubmed.ncbi.nlm.nih.gov/30375165/

  15. Maggi F, Focosi D, Statzu M, Bianco G, Costa C, Macera L, Spezia PG, Medici C, Albert E, Navarro D, Scagnolari C, Pistello M, Cavallo R, Antonelli G. Early Post-Transplant Torquetenovirus Viremia Predicts Cytomegalovirus Reactivations In Solid Organ Transplant Recipients. Sci Rep. 2018 Oct 19;8(1):15490. https://pubmed.ncbi.nlm.nih.gov/30341363/

  16. Strassl R, Schiemann M, Doberer K, Görzer I, Puchhammer-Stöckl E, Eskandary F, Kikic Ž, Gualdoni GA, Vossen MG, Rasoul-Rockenschaub S, Herkner H, Böhmig GA, Bond G. Quantification of Torque Teno Virus Viremia as a Prospective Biomarker for Infectious Disease in Kidney Allograft Recipients. J Infect Dis. 2018 Sep 8;218(8):1191-1199 https://pubmed.ncbi.nlm.nih.gov/30007341/

  17. Kotton CN. Torque Teno Virus: Predictor of Infection After Solid Organ Transplant? J Infect Dis. 2018 Sep 8;218(8):1185-1187 https://pubmed.ncbi.nlm.nih.gov/30007368/

  18. Albert E, Torres I, Talaya A, Giménez E, Piñana JL, Hernández-Boluda JC, Focosi D, Macera L, Maggi F, Solano C, Navarro D. Kinetics of torque teno virus DNA load in saliva and plasma following allogeneic hematopoietic stem cell transplantation. J Med Virol. 2018 Sep;90(9):1438-1443. https://pubmed.ncbi.nlm.nih.gov/29727487/

  19. Kulifaj D, Durgueil-Lariviere B, Meynier F, Munteanu E, Pichon N, Dubé M, Joannes M, Essig M, Hantz S, Barranger C, Alain S. Development of a standardized real time PCR for Torque teno viruses (TTV) viral load detection and quantification: A new tool for immune monitoring. J Clin Virol. 2018 Aug;105:118-127. https://pubmed.ncbi.nlm.nih.gov/29957546/

  20. Wohlfarth P, Leiner M, Schoergenhofer C, Hopfinger G, Goerzer I, Puchhammer-Stoeckl E, Rabitsch W. Torquetenovirus Dynamics and Immune Marker Properties in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation: A Prospective Longitudinal Study. Biol Blood Marrow Transplant. 2018 Jan;24(1):194-199. https://pubmed.ncbi.nlm.nih.gov/29032273/

  21. Focosi D, Antonelli G, Pistello M, Maggi F. Torquetenovirus: the human virome from bench to bedside. Clin Microbiol Infect. 2016 Jul;22(7):589-93. https://pubmed.ncbi.nlm.nih.gov/27093875/

  22. Spandole S, Cimponeriu D, Berca LM, Mihăescu G. Human anelloviruses: an update of molecular, epidemiological and clinical aspects. Arch Virol. 2015 Apr;160(4):893-908. https://pubmed.ncbi.nlm.nih.gov/25680568/

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