Torquetenovirus Serum Load and Long-Term Outcomes in Renal Transplant Recipients

Overview

Journal J Clin Med

Specialty General Medicine

Date 2020 Feb 12

PMID 32041187

Citations 16

Authors

Edmund J Gore

Antonio W Gomes-Neto

Lei Wang

Stephan J L Bakker

Hubert G M Niesters

Anoek A E de Joode

Erik A M Verschuuren

Johanna Westra

Coretta van Leer-Buter

Affiliations

Soon will be listed here.

Abstract

Following transplantation, patients must take immunosuppressive medication for life. Torquetenovirus (TTV) is thought to be marker for immunosuppression, and TTV-DNA levels after organ transplantation have been investigated, showing high TTV levels, associated with increased risk of infections, and low TTV levels associated with increased risk of rejection. However, this has been investigated in studies with relatively short follow-up periods. We hypothesized that TTV levels can be used to assess long term outcomes after renal transplantation. Serum samples of 666 renal transplant recipients were tested for TTV DNA. Samples were taken at least one year after renal transplantation, when TTV levels are thought to be relatively stable. Patient data was reviewed for graft failure, all-cause mortality and death due to infectious causes. Our data indicates that high TTV levels, sampled more than one year post-transplantation, are associated with all-cause mortality with a hazard ratio (HR) of 1.12 (95% CI, 1.02-1.23) per log increase in TTV viral load, ( = 0.02). Additionally, high TTV levels were also associated with death due to infectious causes (HR 1.20 (95% CI 1.01-1.43), = 0.04). TTV levels decrease in the years following renal transplantation, but remain elevated longer than previously thought. This study shows that TTV level may aid in predicting long-term outcomes, all-cause mortality and death due to an infectious cause in renal transplant patients sampled over one year post-transplantation.

Citing Articles

Torque Teno Virus: A Promising Biomarker in Kidney Transplant Recipients.

Dal Lago S, Brani P, Ietto G, Dalla Gasperina D, Gianfagna F, Giaroni C Int J Mol Sci. 2024; 25(14).

PMID: 39062987 PMC: 11277443. DOI: 10.3390/ijms25147744.

Torquetenovirus from bronchoalveolar lavage fluid as a biomarker for lung infection among immunocompromised hosts.

Zhu Z, Wang Y, Ning W, Liu C, Chen C Biomark Med. 2024; 18(13-14):581-591.

PMID: 38982729 PMC: 11370955. DOI: 10.1080/17520363.2024.2366148.

Dynamics of torque teno virus load in kidney transplant recipients with indication biopsy and therapeutic modifications of immunosuppression.

Reineke M, Morath C, Speer C, Rudek M, Bundschuh C, Klein J Front Med (Lausanne). 2024; 11:1337367.

PMID: 38327708 PMC: 10847215. DOI: 10.3389/fmed.2024.1337367.

High-Density Lipoprotein Particles and Torque Teno Virus in Stable Outpatient Kidney Transplant Recipients.

Jonker J, Doorenbos C, Kremer D, Gore E, Niesters H, van Leer-Buter C Viruses. 2024; 16(1).

PMID: 38257843 PMC: 10818741. DOI: 10.3390/v16010143.

Smoking, Alcohol Intake and Torque Teno Virus in Stable Kidney Transplant Recipients.

Doorenbos C, Jonker J, Hao J, Gore E, Kremer D, Knobbe T Viruses. 2023; 15(12).

PMID: 38140628 PMC: 10748022. DOI: 10.3390/v15122387.

References

Gorzer I, Jaksch P, Kundi M, Seitz T, Klepetko W, Puchhammer-Stockl E . Pre-transplant plasma Torque Teno virus load and increase dynamics after lung transplantation. PLoS One. 2015; 10(3):e0122975. PMC: 4404260. DOI: 10.1371/journal.pone.0122975. View

Gorzer I, Jaksch P, Strassl R, Klepetko W, Puchhammer-Stockl E . Association between plasma Torque teno virus level and chronic lung allograft dysfunction after lung transplantation. J Heart Lung Transplant. 2016; 36(3):366-368. DOI: 10.1016/j.healun.2016.10.011. View

Schiemann M, Puchhammer-Stockl E, Eskandary F, Kohlbeck P, Rasoul-Rockenschaub S, Heilos A . Torque Teno Virus Load-Inverse Association With Antibody-Mediated Rejection After Kidney Transplantation. Transplantation. 2016; 101(2):360-367. PMC: 5268087. DOI: 10.1097/TP.0000000000001455. View

Rezahosseini O, Drabe C, Schwartz Sorensen S, Rasmussen A, Perch M, Ostrowski S . Torque-Teno virus viral load as a potential endogenous marker of immune function in solid organ transplantation. Transplant Rev (Orlando). 2019; 33(3):137-144. DOI: 10.1016/j.trre.2019.03.004. View

Maggi F, Bendinelli M . Human anelloviruses and the central nervous system. Rev Med Virol. 2010; 20(6):392-407. DOI: 10.1002/rmv.668. View

Chand S, Atkinson D, Collins C, Briggs D, Ball S, Sharif A . The Spectrum of Renal Allograft Failure. PLoS One. 2016; 11(9):e0162278. PMC: 5029903. DOI: 10.1371/journal.pone.0162278. View

Nishizawa T, Okamoto H, Konishi K, Yoshizawa H, Miyakawa Y, Mayumi M . A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology. Biochem Biophys Res Commun. 1998; 241(1):92-7. DOI: 10.1006/bbrc.1997.7765. View

Maggi F, Focosi D, Statzu M, Bianco G, Costa C, Macera L . Early Post-Transplant Torquetenovirus Viremia Predicts Cytomegalovirus Reactivations In Solid Organ Transplant Recipients. Sci Rep. 2018; 8(1):15490. PMC: 6195516. DOI: 10.1038/s41598-018-33909-7. View

Morrissey P, Reinert S, Yango A, Gautam A, Monaco A, Gohh R . Factors contributing to acute rejection in renal transplantation: the role of noncompliance. Transplant Proc. 2005; 37(5):2044-7. DOI: 10.1016/j.transproceed.2005.03.017. View

10.

Mankotia D, Irshad M . Cloning and expression of N22 region of Torque Teno virus (TTV) genome and use of peptide in developing immunoassay for TTV antibodies. Virol J. 2014; 11:96. PMC: 4032458. DOI: 10.1186/1743-422X-11-96. View

11.

Nishizawa T, Okamoto H, Tsuda F, Aikawa T, Sugai Y, Konishi K . Quasispecies of TT virus (TTV) with sequence divergence in hypervariable regions of the capsid protein in chronic TTV infection. J Virol. 1999; 73(11):9604-8. PMC: 112996. DOI: 10.1128/JVI.73.11.9604-9608.1999. View

12.

Maggi F, Pifferi M, Fornai C, Andreoli E, Tempestini E, Vatteroni M . TT virus in the nasal secretions of children with acute respiratory diseases: relations to viremia and disease severity. J Virol. 2003; 77(4):2418-25. PMC: 141071. DOI: 10.1128/jvi.77.4.2418-2425.2003. View

13.

Youden W . Index for rating diagnostic tests. Cancer. 1950; 3(1):32-5. DOI: 10.1002/1097-0142(1950)3:1<32::aid-cncr2820030106>3.0.co;2-3. View

14.

Macera L, Spezia P, Medici C, Rofi E, Del Re M, Focosi D . Comparative evaluation of molecular methods for the quantitative measure of torquetenovirus viremia, the new surrogate marker of immune competence. J Med Virol. 2019; 94(2):491-498. DOI: 10.1002/jmv.25488. View

15.

Sellares J, de Freitas D, Mengel M, Reeve J, Einecke G, Sis B . Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2011; 12(2):388-99. DOI: 10.1111/j.1600-6143.2011.03840.x. View

16.

Eisenga M, Kieneker L, Soedamah-Muthu S, van den Berg E, Deetman P, Navis G . Urinary potassium excretion, renal ammoniagenesis, and risk of graft failure and mortality in renal transplant recipients. Am J Clin Nutr. 2016; 104(6):1703-1711. DOI: 10.3945/ajcn.116.134056. View

17.

Focosi D, Antonelli G, Pistello M, Maggi F . Torquetenovirus: the human virome from bench to bedside. Clin Microbiol Infect. 2016; 22(7):589-93. DOI: 10.1016/j.cmi.2016.04.007. View

18.

Meier-Kriesche H, Schold J, Srinivas T, Kaplan B . Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant. 2004; 4(3):378-83. DOI: 10.1111/j.1600-6143.2004.00332.x. View

19.

Minovic I, Eisenga M, Riphagen I, van den Berg E, Kootstra-Ros J, Frenay A . Circulating Haptoglobin and Metabolic Syndrome in Renal Transplant Recipients. Sci Rep. 2017; 7(1):14264. PMC: 5660219. DOI: 10.1038/s41598-017-14302-2. View

20.

Burra P, Masier A, Boldrin C, Calistri A, Andreoli E, Senzolo M . Torque Teno Virus: any pathological role in liver transplanted patients?. Transpl Int. 2008; 21(10):972-9. DOI: 10.1111/j.1432-2277.2008.00714.x. View