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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.
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