Torque Teno Virus Load Predicts Opportunistic Infections after Kidney Transplantation but Is Not Associated with Maintenance Immunosuppression Exposure

Abstract

Measuring the non-pathogenic Torque Teno Virus (TTV) load allows assessing the net immunosuppressive state after kidney transplantation (KTx). Currently, it is not known how exposure to maintenance immunosuppression affects TTV load. We hypothesized that TTV load is associated with the exposure to mycophenolic acid (MPA) and tacrolimus. We performed a prospective study including 54 consecutive KTx. Blood TTV load was measured by an in-house PCR at months 1 and 3. Together with doses and trough blood levels of tacrolimus and MPA, we calculated the coefficient of variability (CV), time in therapeutic range (TTR) and concentration/dose ratio (C/D) of tacrolimus, and the MPA-area under the curve (AUC-MPA) at the third month. TTV load at the first and third month discriminated those patients at risk of developing opportunistic infections between months 1 and 3 (AUC-ROC 0.723, 95%CI 0.559–0.905, p = 0.023) and between months 3 and 6 (AUC-ROC 0.778, 95%CI 0.599–0.957, p = 0.028), respectively, but not those at risk of acute rejection. TTV load did not relate to mean tacrolimus blood level, CV, TTR, C/D and AUC-MPA. To conclude, although TTV is a useful marker of net immunosuppressive status after KTx, it is not related to exposure to maintenance immunosuppression.

Evaluation of Torque Teno Virus DNA Load as a Predictive Biomarker in Kidney Transplant Recipients Converted from Calcineurin Inhibitors to Belatacept

“…These results were confirmed by other studies. 26 We observed the same phenomenon after belatacept conversion leading us to hypothesize that during the first 3 months, immunosuppression is higher in relation to the following: (i) loading dose at belatacept introduction and (ii) CNI and mycophenolate mofetil or everolimus coprescriptions. Furthermore, correlation between belatacept concentrations (i.e., through levels) and TTV DNA load have to be assessed in future studies.…”

JC Virus in Kidney Transplant Population: Are We Cautious Enough?

“…Monitoring the Torque Teno Virus (TTV) DNA load in kidney transplant recipients' blood is one of the indirect and non-invasive methods that can indicate overimmunosuppression. However, this method is only available in some resourceful transplant centers [30].…”

Torque Teno Virus (TTV)—A Potential Marker of Immunocompetence in Solid Organ Recipients

“…However, most of the existing studies demonstrate an association between TTV and the incidence of opportunistic infections. In a study relying on 54 renal graft recipients, it was shown that TTV load was higher 1–3 and 3–6 months after transplant among renal graft recipients who suffered from infections [ 17 ]. In a study comprising 221 kidney transplant recipients, the viral loads at 1 month of observation were higher in patients who subsequently developed an infection.…”

“…It was shown that TTV replication is higher in cases of patients with no confirmed humoral or cellular rejection [ 37 , 38 ]. According to research on immunosuppressive drugs, higher levels of immunosuppression and more potent immunosuppressive drugs in most studies are connected with higher TTV loads in renal graft recipients [ 17 ]. Meta-analyses have consistently demonstrated a potential correlation between the TTV and the incidence of opportunistic infections [ 14 , 39 ].…”

“…In children after renal transplant (NTx), the prevalence was as high as 94.5% [ 13 ]. Observations have shown that the number of copies increases after transplantation [ 9 , 10 , 14 , 15 , 16 , 17 , 18 ]. What is especially promising about the role of TTV as a marker of immunosuppression and the risk of graft rejection is that the prevalence and number of copies are unaffected by the current antiviral therapy and prophylaxis used in organ recipients [ 2 ].…”