Quantification of Torque Teno Virus and Epstein-Barr Virus Is of Limited Value for Predicting the Net State of Immunosuppression After Lung Transplantation

Nordén, Rickard; Magnusson, Jesper; Lundin, Anna; Tang, Ka-Wei; Nilsson, Staffan; Lindh, Magnus; Andersson, Lars‐Magnus; Riise, Gerdt C.; Westin, Johan

doi:10.1093/ofid/ofy050

Cited by 30 publications

(41 citation statements)

References 45 publications

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“…In line with previous reports, TTV was detected frequently in donors and recipients, and levels were shown to increase in transplant recipients, which is consistent with prior reports on transplant patients receiving immunosuppressive treatment [34][35][36][37]. Due to low read numbers, it was not possible to assess whether TTV was also transmitted from positive donors to recipients.…”

Section: Parameters Of Renal Function and Jc Polyomavirus Infectionsupporting

confidence: 88%

Metagenomic Virome Sequencing in Living Donor and Recipient Kidney Transplant Pairs Revealed JC Polyomavirus Transmission

Schreiber

Kufner

Hübel

et al. 2018

Clinical Infectious Diseases

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Background. Before kidney transplantation, donors and recipients are routinely screened for viral pathogens using specific tests. Little is known about unrecognized viruses of the urinary tract that potentially result in transmission. Using an open metagenomic approach, we aimed to comprehensively assess virus transmission in living-donor kidney transplantation.Methods. Living kidney donors and their corresponding recipients were enrolled at the time of transplantation. Follow-up study visits for recipients were scheduled 4-6 weeks and 1 year thereafter. At each visit, plasma and urine samples were collected and transplant recipients were evaluated for signs of infection or other transplant-related complications. For metagenomic analysis, samples were enriched for viruses, amplified by anchored random polymerase chain reaction (PCR), and sequenced using high-throughput metagenomic sequencing. Viruses detected by sequencing were confirmed using real-time PCR.Results. We analyzed a total of 30 living kidney donor and recipient pairs, with a follow-up of at least 1 year. In addition to viruses commonly detected during routine post-transplant virus monitoring, metagenomic sequencing detected JC polyomavirus (JCPyV) in the urine of 7 donors and their corresponding recipients. Phylogenetic analysis confirmed infection with the donor strain in 6 cases, suggesting transmission from the transplant donor to the recipient, despite recipient seropositivity for JCPyV at the time of transplantation.Conclusions. Metagenomic sequencing identified frequent transmission of JCPyV from kidney transplant donors to recipients. Considering the high incidence rate, future studies within larger cohorts are needed to define the relevance of JCPyV infection and the donor's virome for transplant outcomes.

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Section: Parameters Of Renal Function and Jc Polyomavirus Infectionsupporting

confidence: 88%

Metagenomic Virome Sequencing in Living Donor and Recipient Kidney Transplant Pairs Revealed JC Polyomavirus Transmission

Schreiber

Kufner

Hübel

et al. 2018

Clinical Infectious Diseases

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“…The replication kinetics observed in our cohort was similar to that previously reported in LT recipients, with a rapid increase in viral load from days 7 to 30, which was followed by a less pronounced slope thereafter, to peak beyond month 3 in most patients. 15,44 It should be noted that the alphatorquevirus doubling time was higher during the first posttransplant week than in the subsequent period until day 30, pointing to a certain delay in the triggering effect of iatrogenic immunosuppression on viral replication and shaping a sigmoid-like curve, which has also been observed after LT. 15 Recent studies have reported an association between low or undetectable alphatorquevirus viremia and an increased risk of graft rejection after lung, 24 kidney, 23 and liver transplantation. 22 Similarly to our experience, data from the Swiss Transplantation Cohort Study showed that 1-year cumulative incidence of rejection among liver transplant recipients with undetectable TTV DNA loads at transplantation were significantly higher than in patients with detectable titers.…”

Section: Discussionmentioning

confidence: 84%

“…15,44 It should be noted that the alphatorquevirus dou- Competitiveness. 15,44 It should be noted that the alphatorquevirus dou- Competitiveness.…”

Section: Discussionmentioning

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

117

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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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“…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 . In the context of solid organ transplantation, a direct association between TTV and CMV infection has been reported in kidney transplantation, whereas a report on lung recipients found no relationship . These conflicting results may be partially explained by the inherent differences between the distinct types of organ transplantation, as well as the various types of immunosuppressive regimens used (and thus the different immunosuppressive burden).…”

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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Quantification of Torque Teno Virus and Epstein-Barr Virus Is of Limited Value for Predicting the Net State of Immunosuppression After Lung Transplantation

Cited by 30 publications

References 45 publications

Metagenomic Virome Sequencing in Living Donor and Recipient Kidney Transplant Pairs Revealed JC Polyomavirus Transmission

Metagenomic Virome Sequencing in Living Donor and Recipient Kidney Transplant Pairs Revealed JC Polyomavirus Transmission

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

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