Massimiliano Bergallo1, Elisa Loiacono2, Stefano Gambarino3, Paola Montanari3, Ilaria Galliano3, Rosanna Coppo2. 1. Department of Public Health and Pediatric Sciences, School of Medicine, University of Turin, Turin, Italy - massimiliano.bergallo@unito.it. 2. Nephrology, Dialysis and Transplantation, Città della Salute e della Scienza di Torino, Regina Margherita Hospital, Turin, Italy. 3. Department of Public Health and Pediatric Sciences, School of Medicine, University of Turin, Turin, Italy.
Abstract
BACKGROUND: Idiopathic nephrotic syndrome (INS) in children is a continuum of clinical disorders characterized by severe proteinuria, dyslipidemia, hypoalbuminemia, and hypercoagulability. It has been hypothesized that toll-like receptors (TLRs) in peripheral blood mononuclear cell might be involved in INS disease. Infections appear to be involved in the onset of INS. The aim of this study was to investigate the expression and function of TLRs in PBMC of INS patients and the relation with two human endogenous retrovirus (HERV), K and W expression. METHODS: The study enrolled 37 children at the exordium and without treatments of minimal-change disease (MCD), the most common single form of nephrotic syndrome (INS) and 20 healthy controls (HC). Relative quantification of target genes expression in patients compared with normal samples was performed with the ΔΔCt method. RESULTS: HERV K and W were expressed in all samples analyzed but the level of expression was much lower in the INS that in HC P<0.0001 and P=0.0002 for HERV-K and -W, respectively. TLR2 was hyperexpressed in 10 vs. 17 (58.8%) of the INS, TLR3 in 3 vs. 17 (17.6%), TLR4 in 12 vs. 17 (70.6%) and TLR9 in 9 vs. 17 (52.9%) (Figure 2). The different expression were statistically significance in the case of TLR2, 3 and 4 (P=0.0183, 0.0218 and 0.0034, respectively) no for TLR9 (P=0.2010). Statistical analysis demonstrated a significance correlation between the low expression of HERV-K and HERV-W and high expression of TLRs. We obtain a statistically significance P<0.0001 considering all TLRs expression in comparison with HERV expression. CONCLUSIONS: We described a down regulation of pol gene of HERV-W and HERV-K mediated by TLRs.
BACKGROUND:Idiopathic nephrotic syndrome (INS) in children is a continuum of clinical disorders characterized by severe proteinuria, dyslipidemia, hypoalbuminemia, and hypercoagulability. It has been hypothesized that toll-like receptors (TLRs) in peripheral blood mononuclear cell might be involved in INS disease. Infections appear to be involved in the onset of INS. The aim of this study was to investigate the expression and function of TLRs in PBMC of INS patients and the relation with two human endogenous retrovirus (HERV), K and W expression. METHODS: The study enrolled 37 children at the exordium and without treatments of minimal-change disease (MCD), the most common single form of nephrotic syndrome (INS) and 20 healthy controls (HC). Relative quantification of target genes expression in patients compared with normal samples was performed with the ΔΔCt method. RESULTS:HERV K and W were expressed in all samples analyzed but the level of expression was much lower in the INS that in HC P<0.0001 and P=0.0002 for HERV-K and -W, respectively. TLR2 was hyperexpressed in 10 vs. 17 (58.8%) of the INS, TLR3 in 3 vs. 17 (17.6%), TLR4 in 12 vs. 17 (70.6%) and TLR9 in 9 vs. 17 (52.9%) (Figure 2). The different expression were statistically significance in the case of TLR2, 3 and 4 (P=0.0183, 0.0218 and 0.0034, respectively) no for TLR9 (P=0.2010). Statistical analysis demonstrated a significance correlation between the low expression of HERV-K and HERV-W and high expression of TLRs. We obtain a statistically significance P<0.0001 considering all TLRs expression in comparison with HERV expression. CONCLUSIONS: We described a down regulation of pol gene of HERV-W and HERV-K mediated by TLRs.
Authors: Elena Morandi; Radu Tanasescu; Rachael E Tarlinton; Dumitru Constantin-Teodosiu; Bruno Gran Journal: Front Immunol Date: 2019-01-22 Impact factor: 7.561