Interferon-Inducible Gene Upregulation Correlates With Successful Viral Clearance in Patients With BK Polyomavirus-Associated Nephropathy.

INTRODUCTION

BK polyomavirus-associated nephropathy (BKPyVAN) remains a challenging complication after kidney transplantation. Although BKPyV-DNAemia is recommended for screening and reducing immunosuppression, reliable predictors of antiviral immune control are needed. The aim of this study was to identify beneficial gene expression patterns, associated with BKPyV-DNAemia clearance, using a commercially available transcriptomic array assay.

METHODS

We retrospectively analyzed RNA-based gene expression patterns in 30 biopsy samples with BKPyVAN, using the NanoString nCounter system. We assessed the relationship between gene expression patterns and subsequent BKPyV-DNAemia dynamics, including viral clearance rates at 6 and 12 months after BKPyVAN diagnosis, as well as the course of intermediate graft function.

RESULTS

Complete BKPyV-DNAemia clearance was observed in 40% of patients (at 6 and 12 months). BKPyV clearance was significantly associated with upregulation of interferon (IFN)- stimulated genes (ISG): ISG15 (log fold change [logFC]: 1.84-2.02), IFN alpha-inducible protein 27 (IFI27) (logFC: 1.46-1.73), IFN-induced protein with tetratricopeptide repeats 1 (IFIT1) (logFC: 1.62-1.87), and IFN-induced transmembrane protein 1 (IFITM1) (logFC: 1.41-1.61). Receiver operating characteristic curve (ROC) analyses revealed areas under the curve (AUCs) of 0.80 to 0.85 for the prediction of DNAemia clearance at 6 months and 0.91 to 0.97 at 12 months (P < 0.01 for both). Higher ISG expression correlated with lower estimated glomerular filtration rate (eGFR) at 6 and 12 months, but not at 24 months. No significant correlations were observed with Banff lesion scores or PVN/AST-IDCOP categories.

DISCUSSION: Significant upregulation of ISGs in kidney allografts with biopsy-proven BKPyVAN was associated with successful clearance of DNAemia. Higher ISG expression correlated with temporarily worsened graft function, which stabilized on longer follow-up. This first exploratory study suggests a potential role for intragraft ISG measurement in monitoring anti-BKPyV immune response.