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

https://doi.org/10.1111/j.1600-6143.2011.03693.xGet rights and content
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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.

Key words:

BKV-associated nephropathy
ELISA
ELISPOT assay
polyomavirus BK

Abbreviations:

Aza
Azathioprine
BKV
polyomavirus BK
BKVN
BKV-associated nephropathy
CNI
calcineurin inhibitor
CsA
Cyclosporine A
Elispot assay
enzyme-linked immunospot assay
IFNG
interferon gamma
KTRs
kidney transplant recipients
LT
Large T-antigen
MMF
mycophenolate mofetil
MP
methylprednisolone
MPA
mycophenolic acid
OPP
overlapping peptide pools
PBMC
peripheral blood mononuclear cells
sBKV-load
serum BKV-load
SCr
serum creatinine
SD
standard deviation
SRL
Sirolimus
st
small t-antigen
Tac
Tacrolimus

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