The effect of BKV reactivation on cytokines behavior in kidney transplanted patients

Zahra Rahimi,Afsoon Afshari,Mohammad Javad Mokhtari,Ramin Yaghobi,Jamshid Roozbeh,Ali Malek Hosseini

doi:10.1186/s12882-021-02645-y

Zahra Rahimi, Afsoon Afshari + Show 4 more

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https://doi.org/10.1186/s12882-021-02645-y

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Abstract

BackgroundBK virus associated nephropathy (BKVAN) is one of the common causes of graft loss among kidney transplanted recipients (KTRs). The current treatment for BKV nephropathy is decreasing the immunosuppressive regimen in KTRs. Interleukin-27 (IL-27) is a multifunctional cytokine that might be the front-runner of an important pathway in this regard. Therefore, in current study it is tried to evaluate the changes in the expression level of IL-27 and some related molecules, resulting from BKV reactivation in KTR patients.MethodsEDTA-treated blood samples were collected from all participants. Patients were divided into two groups, 31 kidney transplant recipients with active and 32 inactive BKV infection, after being monitored by Real time PCR (Taq-Man) in plasma. Total of 30 normal individuals were considered as healthy control group. Real time PCR (SYBR Green) technique is used to determine the expression level of studied genes.ResultsThe results of gene expression comparisons showed that the expression level of IL-27, IFN-γ, TNF-α, TNFR2 and IRF7 genes was significantly higher in inactive group in comparison to active group. The expression level of TLR4 was lower in both active and inactive groups in comparison to control group. ROC curve analysis showed that IL-27 and IRF7 are significantly different amongst other studied genes. Finally, the analyses revealed that the expression level of most of the studied genes (except for TNF-α and TLR4) have significant correlation with viral load.ConclusionsOur findings revealed that IL-27, IFN-γ, TNF-α, TNFR2 and IRF7 expression level is higher in inactive group and TLR4 expression level is lower in patients’ groups in comparison to control group. Also, ROC curve analysis showed IL-27 and IRF7 can significantly differentiate studied groups (BKV active vs. inactive). Therefore, these results might help elucidating the pattern in charge of BKV reactivation in kidney transplanted patients.

Highlights

Due to immunosuppression regimens followed by kidney transplantation (KT), clinically significant reactivation of latent BK polyomavirus (BKV) occurs post-transplantation that might be followed by development of BKV-associated nephropathy (BKVAN)
Studies show that polyfunctional specific BKV T cell responses are important for BKV viruria and viremia in kidney transplant recipients (KTR) [15,16,17,18,19,20,21]
The patients were divided into two groups: 31 kidney transplant recipients with active infection with the age range of 21 to 63 years and 32 without active BKV infection with the age range of 18 to 68 years

Summary

Introduction

Due to immunosuppression regimens followed by kidney transplantation (KT), clinically significant reactivation of latent BK polyomavirus (BKV) occurs (median: 19.5% of KT recipients) post-transplantation that might be followed by development of BKV-associated nephropathy (BKVAN). Studies show that polyfunctional specific BKV T cell (both CD4 and CD8) responses are important for BKV viruria and viremia in KTRs [15,16,17,18,19,20,21]. It is detected that CD4 T cells might have direct controlling capacity through the expression of pro-inflammatory cytokines, including gamma interferon (IFN-γ) and tumor necrosis factor (TNF) and granzyme B molecules. These activities can be executed when there is a lack of CD8 T cell immunity [25]. In current study it is tried to evaluate the changes in the expression level of IL-27 and some related molecules, resulting from BKV reactivation in KTR patients

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