Measurement of Interferon-Gamma Induced Protein 10 in Serum: A Risk Assessment Approach for BKV-Associated Nephropathy

Abstract

Since BKV-associated nephropathy has emerged as a major cause of allograft failure, it has been of importance to identify biomarkers to differentiate between kidney transplant recipients (KTRs) in three sets of clinical situations: (1) KTRs with an increased risk for BKV-reactivation, (2) KTRs with BKV-reactivation and an increased risk for BKV-associated nephropathy, (3) KTRs with BKV-associated nephropathy and an increased risk for progression to allograft failure. We monitored 10 KTRs with prolonged BKV-reactivation/BKV-associated nephropathy, 12 KTRs with self-limited BKV-reactivation, and 17 KTRs without BKV-reactivation in a longitudinal analysis. The extent of immunosuppression was quantified by measures of immune function including lymphocyte subpopulations, interferon-gamma induced protein 10 (IP-10), and adhesion molecules. BKV-specific T-cells were analyzed in an interferon-gamma Elispot assay. BKV-specific antibodies were measured in an ELISA. Although no differences were observed for lymphocyte subpopulations and adhesion molecules, KTRs with self-limited BKV-reactivation showed significantly higher IP-10 levels at the time of diagnosis (p< 0.001) and after recovery from BKV-reactivation (p=0.011) compared to KTRs with prolonged BKV-reactivation and BKV-associated nephropathy. While KTRs with BKV-associated nephropathy didn't show a significant increase of IP-10 levels from diagnosis to recovery from BKV-reactivation (p=0.468), BKV-specific T-cells increased significantly after therapeutic interventions. A cutoff level of 180pg/mL was able to identify KTRs with a risk for BKV-associated nephropathy at diagnosis of BKV-reactivation with a sensitivity of 92.3% and a specificity of 88.9%. Although anti-nonstructural T-cells are suggested as a marker of protection from BKV-reactivation, our data don't provide a characteristic profile to identify KTRs with an increased risk for BKV-reactivation. Assessment of IP-10 differentiates KTRs with an increased risk to progress to BKV-associated nephropathy from KTRs with self-limited BKV-reactivation as soon as at diagnosis of BKV-reactivation. Despite consistently low IP-10, assessment of BKV-specific T-cells identifies recovering BKV-specific immunity in KTRs with BKV-associated nephropathy.