Early BK Polyomavirus-Specific Immunity and Viral Clearance

INTRODUCTION: BK polyomavirus (BKPyV) replication remains a frequent complication after kidney transplantation. The clinical relevance of assessing BKPyV-specific cellular immunity at the time of first detectable viremia remains incompletely defined.

METHODS: We retrospectively studied 50 kidney transplant recipients with a first episode of BKPyV DNAemia who underwent BKPyV-specific interferon-gamma enzyme-linked immunosorbent spot (IFN-γ ELISPOT) shortly after the first positive plasma polymerase chain reaction (PCR). Responses directed against structural (viral protein [VP]1-VP3) and regulatory (large T and small t) antigens were quantified. The primary end point was time from ELISPOT to viral clearance. Secondary end points included viral clearance within 90 days, biopsy-proven BKPyV-associated nephropathy (BKPyVAN), immunosuppression (IS) reduction, and kidney function outcomes.

RESULTS: Structural BKPyV-specific ELISPOT responses showed marked interindividual variability and correlated weakly with viral burden. Thirty-seven patients (74%) achieved viral clearance. Higher structural responses were independently associated with faster viral clearance (adjusted hazard ratio per 100 spot-forming cells [SFC]: 1.28; 95% confidence interval [CI]: 1.15-1.42; P < 0.0001), a lower incidence of biopsy-proven BKPyVAN, and a reduced need for advanced IS reduction (adjusted odds ratio [aOR] per 100 SFC: 0.34; 95% CI: 0.14-0.83; P = 0.018). Responses directed against regulatory antigens showed weaker and less consistent associations with outcomes.

CONCLUSION: Early BKPyV-specific cellular immune responses measured by IFN-γ ELISPOT were consistently associated with viral clearance kinetics and clinically relevant outcomes after kidney transplantation. Structural antigen-specific responses may provide complementary information regarding antiviral immune competence and support further evaluation of immune-stratified management strategies. These findings should be considered hypothesis-generating and require prospective multicenter validation.