BK Virus-Specific Immunity Kinetics: A Predictor of Recovery From Polyomavirus BK-Associated Nephropathy

Abstract

Impaired BKV-specific immunity is associated with development of BKV-associated nephropathy. Suitable immunological parameters to identify patients at risk, however, are still debated. We monitored 18 kidney-transplant recipients through the course of self-limited BKV-reactivation (n = 11) and BKV-associated nephropathy (n = 7). BKV-specific cellular immunity directed to nonstructural small and Large T-antigen, and structural VP1-3 was analyzed in an interferon-γ Elispot assay. BKV-specific IgM and IgG were measured using an enzyme-linked immunosorbent assay simultaneously. BKV-specific cellular immunity directed to five BKV-proteins increased significantly from diagnosis to resolution of BKV-reactivation (p < 0.001). Patients with self-limited BKV-reactivation developed BKV-specific T cells without therapeutic interventions, and cleared BKV-reactivation within a median period of 1 month. Patients with BKV-associated nephropathy, however, showed BKV-specific T cells after a median period of 5 months after therapeutic interventions only, and cleared BKV-reactivation after a median period of 8 months. Anti-structural T cells were detected earlier than anti-nonstructural T cells, which coincided with BKV-clearance. Patients with BKV-associated nephropathy showed the highest frequencies of BKV-specific T cells at recovery, the highest increase in BKV-specific IgG and persistence of increased IgM levels (p < 0.05). Our results suggest prognostic values of BKV-specific immune monitoring to identify those patients at risk of BKV-associated nephropathy and to aid in the management of therapeutic interventions.