Quantitative analysis of BKV-specific CD4+ T cells before and after kidney transplantation.
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.
['Mutlu|Esvet|E|', 'Köksoy|Sadi|S|', 'Mutlu|Derya|D|', 'Yılmaz|Vural T|VT|', 'Koçak|Hüseyin|H|', 'Dinçkan|Ayhan|A|', 'Süleymanlar|Gültekin|G|', 'Gültekin|Meral|M|']
D000328:Adult D000368:Aged D001739:BK Virus D015496:CD4-Positive T-Lymphocytes D015331:Cohort Studies D005260:Female D006801:Humans D007371:Interferon-gamma D007668:Kidney D016030:Kidney Transplantation D008297:Male D008875:Middle Aged D008991:Monitoring, Physiologic D027601:Polyomavirus Infections D014412:Tumor Virus Infections D014775:Virus Activation
BKV ELISPOT Mixture of overlapping peptide pool Renal transplantation