Clinical Problem and hypothesis: Antibody mediated rejection (ABMR) is a cardinal cause of late graft failure after kidney transplantation (KTX). A promising predictive diagnostic tool is the quantification of the plasma load of the apathogenic Torque Teno virus (TTV) which might mirror the level of immunosuppression and thus reflect the risk of rejection.

Methods: In this prospective study (cross-sectional screening after a median of 6.3 years post-transplantation in the context of an ongoing interventional trial, NCT01873157) 715 adult patients with a functioning kidney allograft >6 months post-transplantation (eGFR >20mL/min/1.73m²) were subjected to RT-PCR based TTV quantification and bead array-based screening for anti-HLA donor specific antibodies (DSA). DSA positive patients were subjected to protocol biopsies.

Results: TTV (>2log₁₀ copies/mL) was detected in 678 of the 715 patients (95%) with a median of 2.3×10⁵ (IQR 1.9×10⁴-1.9×10⁶). TTV load was highest in the first year after transplantation with a median of 3.4×10⁶ (IQR 1.4×10⁵-8.7×10⁷; P<0.001). TTV load was higher after induction therapy (P<0.001) and in patients on tacrolimus-based immunosuppression (P=0.002). Among the 86 DSA+ recipients, 46 patients (53%) were diagnosed with ABMR according to the Banff 2013 scheme. ABMR+ patients had significantly lower TTV loads (median, IQR; 6.6×10⁴, [IQR 3.0×10³-7.2×10⁵]) than patients without ABMR (N=669; 2.6×10⁵, [IQR 2.2×10⁴-2.1×10⁶]; P=0.003; risk ratio for TTVlog, 0.91, 95% confidence interval [CI], 0.87 to 0.96; P=0.001). Bivariate analysis revealed a robust and linear inverse association of TTV with the diagnosis of ABMR independently of time of screening and other predictors of ABMR. Adjusted risk ratio for TTVlog in a multivariate model was 0.94 (95% CI 0.90 to 0.99; P=0.016). Similar results were obtained in a subgroup analysis restricted to the 86 patients subjected to a protocol biopsy, where TTV load in ABMR- patients was higher compared to ABMR+ patients (N=40; 4.5×10⁵, [IQR 4.3×10⁴– 3.9×10⁶]; P=0.001).

Conclusion and outlook: Our results demonstrate a lower TTV load in KTX patients with ABMR. Monitoring of TTV load could represent a useful novel tool for early therapeutic intervention to prevent late ABMR and graft loss.

CITATION INFORMATION: Bond G, Schiemann M, Eskandary F, Herkner H, Puchhammer E, Oberbauer R, Böhmig G. Torque Teno Virus – Inverse Association with Late Silent Antibody Mediated Kidney Allograft Rejection. Am J Transplant. 2016;16 (suppl 3).

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