Torque Teno Virus Viral Load as a Marker of Immune Function in Allogeneic Haematopoietic Stem Cell Transplantation Recipients

Abstract

Torque teno virus (TTV) has been proposed as a surrogate biomarker of T-cell function in allogeneic–haematopoietic–stem-cell transplantation (allo-HSCT). Conflicting data exists regarding the value of TTV to assess the degree of immunosuppression. The aim of the present study was to investigate the correlation between TTV viral load and immune function. Using samples from a prospective cohort composed of healthy-volunteers (HV) and allo-HSCT recipients at 6 months post-transplantation, we assessed the correlation between TTV viraemia and immune cell counts or T-cell proliferation capacity post-phytohaemagglutinin stimulation. TTV viraemia was detected in 68% of HV (n = 80) and 100% of allo-HSCT recipients (n = 41; p < 0.001); it was significantly higher in allo-HSCT recipients (3.9 vs. 2.1 Log copies/mL, p < 0.001). There was no correlation between T-cell function and CD3+T-cell count (rho: 0.002) suggesting that T-cell count can normalise without full functional recovery. Furthermore, no significant correlation was observed between TTV viraemia and absolute total/subset lymphocyte counts (rho: <0.13). The highest correlation was observed between TTV viral load and T-cell proliferation capacity (rho: −0.39). We therefore report an inverse correlation between T-cell function and TTV viraemia that is independent of T-cell count. Monitoring of TTV viraemia could be a fast suitable option to objectively assess the competence of immune function in at-risk populations.

Viruses, friends, and foes: The case of Torque Teno Virus and the net state of immunosuppression

“…92,96 Thereafter, some 94,97 but not all studies 95 found an inverse correlation between TTV load and absolute lymphocyte counts, which would point to the restoration of TTV-specific immunity. In support of this hypothesis, some authors have reported that viral loads after engraftment inversely correlated with the T-cell proliferative capacity 91 or directly with the number of CD8+CD57+ T-cells (which are considered as hallmarks of immunosenescence). 93 The median TTV-AUC between days 90 and 210 was significantly higher in patients that received corticosteroids for the treatment of GvHD within this period.…”

“…89 In line with the SOT population, TTV loads are significantly higher in allo-HSCT recipients than in healthy subjects. [90][91][92] Post-transplant kinetics is usually characterized by a rapid increase of DNA levels during the first 2-3 months, to peak by day 100 and maintain through the first year or progressively return to baseline levels. 91,[93][94][95][96][97] This evolution is roughly comparable to that observed after SOT.…”

“…[90][91][92] Post-transplant kinetics is usually characterized by a rapid increase of DNA levels during the first 2-3 months, to peak by day 100 and maintain through the first year or progressively return to baseline levels. 91,[93][94][95][96][97] This evolution is roughly comparable to that observed after SOT. Recipients with lymphoid malignancies consistently show higher loads, both at baseline and throughout the early post-transplant period, that those with an underlying myeloid malignancy.…”

“…96 These results contrast with other studies in which allo-HSCT recipients experiencing viral opportunistic infection (including CMV) display higher TTV loads. 91 For instance, Gilles et al showed that recipients developing viral reactivation (CMV, EBV, or BKPyV) and/or GVHD during the first 100 days after transplantation had a significantly higher TTV load by day 30 than those with an uncomplicated course (median of 1.8 × 10 9 vs. 2.5 × 10 6 copies/ml; P-value = 0.005). 92 Wohlfarth et al observed significant correlations between TTV and CMV (Rho = 0.39; P-value < 0.01) and EBV DNA levels (Rho = 0.45; P-value = 0.02) during episodes of viremia.…”

Human Anelloviruses: Prevalence and Clinical Significance During Pregnancy

“…Whether this means that anelloviruses have a role in enabling pathological viral infections remains to be elucidated. Given the prevalence of TTV in organ transplant recipients, TTV load has been suggested as a candidate indicator of immune suppression (35)(36)(37).…”