Divergent Cellular and Humoral Immunity to BK Polyomavirus in Healthy Adults and Renal Transplant Recipients Based on Blood and Urine Samples: Implications for Immune-Guided Monitoring

Background/Objectives: BK polyomavirus (BKPyV) establishes lifelong, asymptomatic persistence but frequently reactivates in renal transplant recipients, contributing to significant post-transplant morbidity. Although humoral responses are routinely monitored, the role of cellular immunity in viral control remains incompletely characterized. This study aimed to characterize BKPyV-specific T-cell responses and IgG-binding levels in healthy adults and renal transplant recipients and to explore their association with active BKPyV viruria. Methods: BKPyV DNA was screened and quantified in urine samples from eighty-two healthy adults and thirty-three renal transplant recipients, who were categorized into active, no, historical, and pre-transplant infection groups. BKPyV-specific cellular immunity was assessed in peripheral blood mononuclear cells using IFN-γ ELISPOT and T-cell proliferation assays, and IgG binding levels were measured in plasma using semi-quantitative ELISA. Results: Healthy BKPyV-positive individuals had significantly higher IFN-γ-secreting T-cell frequencies than BKPyV-negative individuals, with no significant difference in IgG levels. Transplant recipients with detectable viruria had markedly diminished IFN-γ responses compared with all other groups, whereas IgG levels remained comparable except in the pre-transplant group (n = 2). A strong negative correlation was observed between IgG levels and urine viral load in actively infected patients. Proliferation assays showed no detectable antigen-specific proliferation despite measurable cytokine secretion. Conclusions: Cellular immunity, rather than total binding IgG levels, may be more closely associated with BKPyV activity, particularly in transplant recipients. Given the exploratory cross-sectional design, prospective validation is needed. These findings support integrating cell-mediated immune assays into BKPyV monitoring to improve post-transplant risk assessment.