Quantitative analysis of BKV-specific CD4+ T cells before and after kidney transplantation

Abstract

Background: BK virus (BKV) is the main infectious cause of renal allograft dysfunction. Although recent studies showed an inverse correlation between BKV-specific T-cell responses and viral load after transplantation, the importance of pre-transplant response in the process of virus reactivation has only been studied once. In this study, we aimed to determine whether pre-transplant CD4+ T-cell response can be used for prediction of BKV reactivation and BKV nephropathy (BKVN), by a method that can practically be used in routine patient monitoring.

Methods: BKV-specific CD4+ T-cell responses of 31 kidney recipients (all from live donors) were measured by an IFN-γ-enzyme-linked-immunospot (ELISPOT) method using mixture of peptides, at day 0 and +1, +3, and +6 months posttransplant. Additionally, seven other reactivation patients as another group were also analyzed. BKV viral loads in plasma were measured by real-time polymerase chain reaction (PCR). Responses of 10 healthy people were also included as controls in the analysis.

Results: All but one patient and all of the controls had detectable CD4+ T-cell responses. Reactivation occurred in 8 out of 31 patients. There was no significant association between pretransplant BKV-specific CD4+ T-cell responses and BKV reactivation and between BKV DNA levels and CD4+ T-cell responses. In the additional group consisting of reactivation patients, four patients who had BKVN showed negative correlation between BKV-DNA levels and BKV-specific CD4+ T-cell responses (p<0.05). One patient who developed BKVN, however, was not able to mount a similar CD4+ T-cell response to viral reactivation despite immunosuppressive reduction.

Conclusion: Even though our cohort is small, our results may suggest that pre-transplant measurement of BKV specific CD4+ T-cell response may not be necessary, and that post-transplant monitoring, particularly during reactivation, may be more helpful in the management of the infection.

Keywords: BKV; ELISPOT; Mixture of overlapping peptide pool; Renal transplantation.