Immune Monitoring in BK Viurs Nephropathy: How to Identify Patients at the Highest Risk.

Abstract

Quantification of BKV-load and BKV-specific immunity have been evaluated to monitor BKV-replication and progression to BKV-associated nephropathy. Previous studies, however, failed to identify immune markers characterizing kidney transplant recipients (KTRs) at increased risk of BK viremia. Here, we studied all adult KTRs at our single transplant center transplanted between 2007 and 2011. 42 (10%) of 425 KTRs were diagnosed with BK viremia within the first 6 months after renal transplantation. An age- and gender-matched control group of 127 KTRs without BK viremia was used for comparison. Samples were collected before transplantation and at +1, +2, and +3 months posttransplantation. BKV-specific T-cells directed to VP1 and Large T-antigen and CMV-specific T-cells directed to pp65 and IE-1, were measured using an interferon-γ Elispot assay. The extent of immunosuppression was quantified by measures of immune function including lymphocyte subpopulations and serum cytokine levels. KTRs developing early BKV-replication showed significantly increased frequencies of BKV-specific T-cells directed to Large T-antigen prior to transplantation compared to the control group (p<0.001). Interestingly, BKV-specific T-cells directed to Large T-antigen were significantly higher compared to VP1 (p=0.042). Shortly after transplantation, however, BKV-specific T-cells were significantly decreased or undetectable in KTRs developing BK viremia (p<0.001). In addition CD3+, CD4+, and CD8+ T-cell counts, and interferon-γ serum levels were significantly lower in KTRs with BK viremia at +1 month after transplantation (p<0.05). KTRs developing BK viremia showed lower CMV-specific T-cells prior to transplantation compared to the control group (p=0.048). Our results suggest that BKV-specific cellular immunity is triggered by subclinical activation of BKV infection prior to transplantation. In KTRs developing BK viremia identified risk factors and overimmunosuppression result in a decline of BKV-specific T-cells insufficient to further regulate BKV-replication. Our data indicate that BK viremia may result at least in part from recipient origin, and supports immune monitoring prior to transplantation to identify KTRs at the highest risk.