Relationship Between Interleukin-2 Polymorphism and BK Virus Infection After Kidney Transplantation.

Abstract

Background: BK virus (BKV) can cause BKV nephropathy, which affects up to 10% of renal transplant recipients (RTRs), causing allograft dysfunction and graft loss. Cytokines such as tumor necrosis factor- α (TNF-α), interleukin-10 (IL10), and interleukin-2 (IL2) have been shown to possess antiviral properties and their polymorphisms are associated with disease outcome. We assessed the impact of IL10, IL2, and TNF-α gene polymorphisms on the risk of BKV infection. Methods: IL2-330 G>T; IL10 -1082 A>G; and TNF-α -308 A>G gene polymorphisms were studied in 233 RTRs (58 RTRs with BKV and 175 without BKV), using DNA-based polymerase chain reaction with sequence-specific primers and restriction. We then examined the functionality of these promoter genetic variants by luciferase assay and enzyme-linked immunosorbent assay (ELISA). Results: IL2-330 TT was associated with an increased risk of BKV infection (OR=2.9, 95% CI=1.2-6.5, p=0.01) while IL2-330 GG genotype was associated with a reduced risk of BKV infection (OR=0.34, 95% CI=0.13-0.87, p=0.01). In luciferase reporter assay, IL2-330 G allele tended to enhance the transcriptional activity of IL2 with an approximately 1.6-fold over T allele. Furthermore, ELISA tests showed that when peripheral blood mononuclear cells (PBMCs) were stimulated in culture with peptide pools encompassing BKV, there was a significant increase in IL2 response. There was no significant association between the allelic as well as genotypic frequencies of IL10 -1082 A>G and TNF-α -308 A>G gene polymorphisms with BKV infection. Conclusions: These results suggested that IL2-330 TT/T was associated with an increased risk, but IL330 GG/G was associated with reduced risk of BKV infection. This SNP, which effectively influenced the expression of IL2, may be a new biomarker to assist risk of BKV infection.