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.