Torquetenovirus Dynamics and Immune Marker Properties in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation: A Prospective Longitudinal Study

Abstract

Torquetenovirus (TTV) has been proposed as a marker of immune function in patients receiving immunosuppression after solid organ transplantation. This study aimed to define TTV plasma dynamics and investigate clinical associations in patients following allogeneic hematopoietic stem cell transplantation (HSCT). This was a single-center prospective longitudinal study involving 50 consecutive patients treated with HSCT between March 2015 and April 2016. TTV plasma DNA levels were measured with quantitative PCR at 12 consecutive time points during the first year after HSCT. Forty of the 50 patients (80%) had detectable TTV viremia before HSCT (median level, 5.37 log10 copies/mL; interquartile range [IQR], 3.51-6.44 log10 copies/mL). All patients subsequently developed TTV viremia during the follow-up period. Plasma viral loads evolved dynamically over time, with a peak of 8.32 log10 copies/mL (IQR, 7.33-9.35 log10 copies/mL) occurring at 79 days (IQR, 50-117 days) following HSCT and a stable plateau toward the end of the follow-up period. The type of malignancy, the use of antithymocyte globulin during conditioning, and the occurrence of acute graft-versus-host disease requiring systemic therapy had temporary effects on TTV dynamics. TTV levels showed a significant correlation with absolute lymphocyte counts following engraftment (r = -.27; P < .01) and with cytomegalovirus (CMV; r=.39; P < .01) and Epstein-Barr virus (EBV; r=.45; P = .02) viral loads during phases of viremia. Immune-related clinical events were not predicted by TTV levels. TTV viremia occurred universally and was sustained throughout the first year after HSCT. Several variables and events before and after HSCT were correlated with TTV levels and hint toward immune marker properties of TTV, but their complex interactions might perturb the capability of TTV to predict immune-related complications in this population.

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

“…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 . 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 .…”

“…(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. (23) 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).…”

Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children

“…Interestingly, a number of typically nonpathogenic viruses such as Torquetenovirus and KI Polyomavirus were present in more than half of the cohort. While data supporting the direct pathogenicity of these viruses are lacking, they may indicate immune dysfunction and predict numerous post-transplant infectious and alloimmune complications [60][61][62]. Future studies aimed at characterizing longitudinal changes in the pulmonary virome of immunocompromised children are warranted.…”

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

“…Moreover, the area under a curve of plasma TTV DNA loads between days +20 and +30 after allo‐HSCT allows the estimation of the risk of high‐level cytomegalovirus DNAemia . Nevertheless, the available data also suggest that once the TTV DNA load reaches a plateau, its magnitude may reflect the net state of immunosuppression, as rising plasma TTV DNA levels are seen in episodes of severe acute graft‐versus‐host disease requiring corticosteroid therapy at high doses …”

“…7 Nevertheless, the available data also suggest that once the TTV DNA load reaches a plateau, its magnitude may reflect the net state of immunosuppression, as rising plasma TTV DNA levels are seen in episodes of severe acute graft-versus-host disease requiring corticosteroid therapy at high doses. 5,6,8,9 Although T lymphocytes appear to be the main target for TTV replication, 10,11 other cell types of nonhematopoietic origin may also be fully permissive, thus potentially contributing to the TTV burden. 1,2 Pertinent to this study, TTV DNA is frequently detected in saliva from TTV-infected healthy individuals.…”