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

Albert, Eliseo; Solano, Carlos; Giménez, Estela; Focosi, Daniele; Pérez, Ariadna; Macera, Lisa; Piñana, José Luís; Boluda, Juan Carlos Hernández; Maggi, Fabrizio; Navarro, David

doi:10.1038/bmt.2017.235

Cited by 33 publications

(69 citation statements)

References 36 publications

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“…14,39-41 We observed a direct correlation, although weak, between recipient age and plasma DNA loads, in line with previous studies performed in healthy adults. 19, 36 We did not replicate, however, such findings since the use of ATG as induction therapy in our cohort was associated with higher viral loads and lower doubling viral times during the first posttransplant months. 9 Both findings would support the immunosuppression, we observed a negative correlation between plasma loads and CD3+, CD4+, and CD8+ T cell counts assessed at months 1 and 3.…”

Section: Discussioncontrasting

confidence: 65%

“…6 Torque teno virus (TTV), first isolated in 1997 from a Japanese patient with posttransfusion hepatitis, 7 constitutes the prototype member within the Anelloviridae family. 10,11 Immunosuppressive therapy for solid organ transplantation (SOT), 12-15 postengraftment phase after allogeneic hematopoietic stem-cell transplantation, [16][17][18][19] or CD4 + T cell depletion in human immunodeficiency virus (HIV) infection 20,21 lead to an evident increase in alphatorquevirus DNA loads that would in turn correlate with the overall amount of immunosuppression. TTV infection is thought to be acquired in childhood via multiple routes (transplacental, respiratory, fecal-oral, or transfusion) and reaches a prevalence as high as 90% among the adult population.…”

Section: Introductionmentioning

confidence: 99%

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Monitoring of alphatorquevirus DNA levels for the prediction of immunosuppression-related complications after kidney transplantation

Fernández‐Ruiz

Albert

Giménez

et al. 2019

American Journal of Transplantation

106

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The replication kinetics of nonpathogenic anelloviruses belonging to the Alphatorquevirus genus (such as torque teno virus) might reflect the overall state of posttransplant immunosuppression. We analyzed 221 kidney transplant (KT) recipients in whom plasma alphatorquevirus DNA load was quantified by real-time polymerase chain reaction at baseline and regularly through the first 12 posttransplant months. Study outcomes included posttransplant infection and a composite of opportunistic infection and/or de novo malignancy (immunosuppression-related adverse event [iRAE]). Alphatorquevirus DNA loads at month 1 were higher among patients who subsequently developed posttransplant infection (P = .023) or iRAE (P = .009). Likewise, those with iRAE beyond months 3 and 6 also exhibited higher peak viral loads over the preceding periods. Areas under the curve for log 10 alphatorquevirus DNAemia estimated by months 1 or 6 were significantly higher in patients experiencing study outcomes. Alphatorquevirus DNA loads above 3.15 and 4.56 log 10 copies/mL at month 1 predicted the occurrence of posttransplant infection (adjusted hazard ratio [aHR]: 2.88; 95% confidence interval [CI]: 1.13-7.36; P = .027) and iRAE (aHR: 5.17; 95% CI: 2.01-13.33; P = .001). In conclusion, posttransplant monitoring of plasma alphatorquevirus DNA kinetics may be useful to identify KT recipients at increased risk of immunosuppression-related complications. K E Y W O R D S biomarker, clinical research/practice, complication: infectious, complication: malignant, infection and infectious agents, infection and infectious agents -viral, infectious disease, kidney transplantation/nephrology

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Section: Discussioncontrasting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Monitoring of alphatorquevirus DNA levels for the prediction of immunosuppression-related complications after kidney transplantation

Fernández‐Ruiz

Albert

Giménez

et al. 2019

American Journal of Transplantation

106

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“…In the setting of allogeneic stem cell transplantation, Albert et al showed an inverse association between TTV viremia and CMV infection, whereas no overall correlation was found between TTV DNA and CMV DNA. (21) Wohlfarth et al, in turn, showed a direct link between TTV DNA and CMV infection, as well as a linear correlation between the DNA of both viruses. (22) In the context of solid organ transplantation, a direct association between TTV and CMV infection has been reported in kidney transplantation, (19) whereas a report on lung recipients found no relationship.…”

Section: Discussionmentioning

confidence: 96%

“…Regarding the interaction between CMV and TTV, conflicting results have been reported in the literature. In the setting of allogeneic stem cell transplantation, Albert et al showed an inverse association between TTV viremia and CMV infection, whereas no overall correlation was found between TTV DNA and CMV DNA . Wohlfarth et al, in turn, showed a direct link between TTV DNA and CMV infection, as well as a linear correlation between the DNA of both viruses .…”

Section: Discussionmentioning

confidence: 99%

Torque Teno Virus Is Associated With the State of Immune Suppression Early After Liver Transplantation

et al. 2019

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The development of noninvasive biomarkers that reflect the state of immunosuppression (IS) remains an unmet need in liver transplantation (LT). Torque Teno virus (TTV) is a highly prevalent, nonpathogenic DNA virus whose plasma levels may be associated with the immune status of the host. The aim of this study was to assess the role of TTV as a biomarker of IS in LT recipients. TTV DNA in plasma was quantified by real‐time polymerase chain reaction at different time points during the first year after transplant in a prospectively followed cohort of 63 de novo LT recipients, and any correlation between TTV DNA and biopsy‐proven acute cellular rejection (ACR) and opportunistic infections was then evaluated. In addition, TTV DNA was studied in 10 longterm LT recipients in monotherapy with tacrolimus, 10 tolerant recipients, and 10 healthy controls. TTV was detected in the plasma of all patients. Among the 63 LT recipients, 20 episodes of ACR were diagnosed, and there were 28 opportunistic infections, 26 of them being cytomegalovirus (CMV) infections. TTV viremia was significantly lower during ACR (4.41 versus 5.95 log10 copies/mL; P = 0.002) and significantly higher during CMV infections (5.79 versus 6.59 log10 copies/mL; P = 0.009). The area under the receiver operating characteristic curve of TTV viral load for the diagnosis of moderate ACR was 0.869, with a sensitivity and negative predictive value of 100%, respectively, for a cutoff point of 4.75 log10 copies/mL. There were no statistically significant differences in TTV DNA in either longterm or tolerant patients and healthy controls. In conclusion, plasma TTV DNA levels are associated with immune‐related events after LT and could constitute a potential biomarker of the state of IS during the first months after transplant.

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“…PCR amplification and amplicon detection were done on the ABI Prism 7500 system (PE Biosystems, Foster City, CA). Sample processing for TTV DNA quantitation on plasma samples was previously described . The limit of quantitation of the PCR assay was around 25 copies/mL and the limit of detection, approximately 10 copies/mL (75% repeatability).…”

Section: Methodsmentioning

confidence: 99%

Kinetics of torque teno virus DNA load in saliva and plasma following allogeneic hematopoietic stem cell transplantation

Albert

Torres

Talaya

et al. 2018

Journal of Medical Virology

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Plasma torque teno virus (TTV) DNA load directly correlates with the degree of T-cell immune reconstitution early after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, the kinetics of oral TTV DNA shedding was examined to assess whether quantitation of TTV DNA load in saliva may either replace or complement that in plasma for predicting lymphocyte (ALC) reconstitution after engraftment. This prospective observational study enrolled 38 nonconsecutive allo-HSCT recipients. Saliva and plasma specimens were collected at baseline (pretransplant) and at around days +30, +50, and +90 after allo-HSCT. TTV DNA was quantitated in both specimen types by real-time PCR. ALCs were measured by cytometry. A total of 104 paired saliva and plasma specimens were available for TTV PCR analyses. TTV DNA was detected more frequently in saliva than in plasma specimens at all time points (overall, 94.2% vs 86.5%). Increasing levels of TTV DNA were seen in both specimen types from day +30 to day +90 after transplantation. Overall, TTV DNA loads were significantly higher in saliva than in plasma specimens (P = .0002) and correlated significantly (P ≤ .0001). A direct correlation between TTV DNA loads in saliva and plasma and ALCs was observed after engraftment (P = .034 and P = .002, respectively). Future studies should be aimed at determining whether monitoring of oral TTV DNA shedding may be of any utility for inference of immune reconstitution after allo-HSCT.

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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

Cited by 33 publications

References 36 publications

Monitoring of alphatorquevirus DNA levels for the prediction of immunosuppression-related complications after kidney transplantation

Monitoring of alphatorquevirus DNA levels for the prediction of immunosuppression-related complications after kidney transplantation

Torque Teno Virus Is Associated With the State of Immune Suppression Early After Liver Transplantation

Kinetics of torque teno virus DNA load in saliva and plasma following allogeneic hematopoietic stem cell transplantation

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