Abstract
Objective: Human BK virus (BKV) is a member of the polyomavirus family. In renal transplant recipients, reactivation of BKV may cause the renal-allograft dysfunction. Primary BKV infection usually occurs asymptomatically during childhood. After primer infection, BKV persists latently especially in the urogenital system. Cellular immunity plays an important role in the pathogenesis of BKV infection. The aim of this study was to determine the urinary cytokine responses in patients with BKV infection and associated levels of urinary cytokines and BK viruria. Methods: Urine samples of 72 patients with BKV infection were included in this study. BKV DNAs were detected by using quantitative real-time polymerase chain reaction. The levels of cytokines in urine samples were determined by ELISA. Results: The levels of urinary proinflammatory cytokines in BKV DNA positive patients were significantly higher than those of patients who were BKV DNA negative. In addition, urinary proinflammatory cytokines were also higher in BKV DNA positive patients with high viral load than in patients with low viral load. Conclusion: According to our results, it is suggested that proinflammatory cytokines may play an important role in the pathogenesis of BKV infections. A better understanding of cytokine responses in BKV infections may help to provide new therapeutic approaches to the treatment of BKV infection especially in transplantation patients.
Highlights
BK viruria did not change the levels of IL-6, TNF-α as compared to the BK virus (BKV) DNA negative group (p>0.05)
Urinary proinflammatory cytokines were higher in the BKV DNA positive patients with a high viral load than in patients with a low viral load (p
Our data indicated that patients with significant BK viruria show signs of proinflammatory responses with the induction of IL-2, IL-23, and IFN-γ, which results in increased urinary levels of these cytokines
Summary
Patients We assessed BKV-DNA viral load in urine samples of 72 patients. Urine BKV DNA load was measured by using the quantitative real-time polymerase chain reaction (real-time PCR) (Qiagen, Hamburg, Germany). BKV DNA extraction Viral DNAs were extracted using the MagAttract Virus Mini M48 kit (Qiagen, Hamburg, Germany) on the BioRobot M48 workstation (Qiagen, Hamburg, Germany) following the manufacturer's instructions. Real-time quantative PCR: BKV DNA load was measured by quantitative real-time PCR. Quantification of viral DNA load in urine samples was performed using the Qiagen Artus BKV RG PCR kit (Qiagen, Hamburg). Data analysis was performed with the RotorGene software according to the manufacturer’s instructions. Cytokine measurement Urine interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-23 (IL-23), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), transforming growth factor (TGF-β) levels were determined by commercial enzyme-linked immunosorbent assay (ELISA) kits according to the manifacturer’s instructions (Biosource, California, USA). The Bonferroni test was used as a Post Hoc analysis. p
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