Torque Teno Virus Load—Inverse Association With Antibody-Mediated Rejection After Kidney Transplantation

Schiemann, Martin; Puchhammer‐Stöckl, Elisabeth; Eskandary, Farsad; Kohlbeck, Philip; Rasoul‐Rockenschaub, Susanne; Heilos, Andreas; Kozakowski, Nicolas; Görzer, Irene; Kikić, Željko; Herkner, Harald; Böhmig, Georg A.; Bond, Gregor

doi:10.1097/tp.0000000000001455

Cited by 86 publications

(118 citation statements)

References 37 publications

(54 reference statements)

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“…(8) Similarly, low TTV viremia has been linked to a higher incidence of chronic allograft dysfunction in lung transplantation (15) and with antibody-mediated rejection in kidney transplantation. (16) Our results suggest a higher state of IS in patients who received triple IS: These patients presented significantly more episodes of CMV infection and had higher TTV DNA levels. In addition, all episodes of CMV disease were diagnosed in this group.…”

Section: Discussionmentioning

confidence: 57%

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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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Section: Discussionmentioning

confidence: 57%

“…Regarding posttransplant events in LT, negative viremia before transplant has been associated with a higher incidence of rejection . Similarly, low TTV viremia has been linked to a higher incidence of chronic allograft dysfunction in lung transplantation and with antibody‐mediated rejection in kidney transplantation …”

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 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: 99%

“…[22][23][24] In addition, some authors have reported a direct association between higher DNA loads and posttransplant infection. [22][23][24] In addition, some authors have reported a direct association between higher DNA loads and posttransplant infection.…”

Section: Introductionmentioning

confidence: 99%

“…It has been suggested that replication kinetics for alphatorquevirus might be a useful tool to identify SOT recipients at increased risk of graft rejection (ie, those with lower DNA loads). [22][23][24] In addition, some authors have reported a direct association between higher DNA loads and posttransplant infection. 25 Nevertheless, most of these studies had small sample sizes or were exclusively focused on graft rejection as study outcome.…”

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

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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Metagenomic analysis of DNA viruses from posttransplant lymphoproliferative disorders

et al. 2019

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Posttransplant lymphoproliferative disorders (PTLDs), 50%‐80% of which are strongly associated with Epstein‐Barr virus (EBV), carry a high morbidity and mortality. Most clinical/epidemiological/tumor characteristics do not consistently associate with worse patient survival, so our aim was to identify if other viral genomic characteristics associated better with survival. We extracted DNA from stored paraffin‐embedded PTLD tissues at our center, identified viral sequences by metagenomic shotgun sequencing (MSS), and analyzed the data in relation to clinical outcomes. Our study population comprised 69 PTLD tissue samples collected between 1991 and 2015 from 60 subjects. Nucleotide sequences from at least one virus were detected by MSS in 86% (59/69) of the tissues (EBV in 61%, anelloviruses 52%, gammapapillomaviruses 14%, CMV 7%, and HSV in 3%). No viruses were present in higher proportion in EBV‐negative PTLD (compared to EBV‐positive PTLD). In univariable analysis, death within 5 years of PTLD diagnosis was associated with anellovirus (P = 0.037) and gammapapillomavirus (P = 0.036) detection by MSS, higher tissue qPCR levels of the predominant human anellovirus species torque teno virus (TTV; P = 0.016), T cell type PTLD, liver, brain or bone marrow location. In multivariable analyses, T cell PTLD (P = 0.006) and TTV PCR level (P = 0.012) remained significant. In EBV‐positive PTLD, EBNA‐LP, EBNA1 and EBNA3C had significantly higher levels of nonsynonymous gene variants compared to the other EBV genes. Multiple viruses are detectable in PTLD tissues by MSS. Anellovirus positivity, not EBV positivity,was associated with worse patient survival in our series. Confirmation and extension of this work in larger multicenter studies is desirable.

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Torque Teno Virus Load—Inverse Association With Antibody-Mediated Rejection After Kidney Transplantation

Cited by 86 publications

References 37 publications

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

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

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

Metagenomic analysis of DNA viruses from posttransplant lymphoproliferative disorders

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