Bergallo Massimiliano, Loiacono Elisa, Gambarino Stefano, Montanari Paola, Galliano Ilaria, Coppo Rosanna
Department of Public Health and Pediatric Sciences, School of Medicine, University of Turin, Turin, Italy -
Nephrology, Dialysis and Transplantation, Città della Salute e della Scienza di Torino, Regina Margherita Hospital, Turin, Italy.
Minerva Urol Nefrol. 2017 Apr;69(2):201-208. doi: 10.23736/S0393-2249.16.02658-8. Epub 2016 Jun 29.
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.
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.
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.
We described a down regulation of pol gene of HERV-W and HERV-K mediated by TLRs.
儿童特发性肾病综合征（INS）是一系列临床病症，其特征为严重蛋白尿、血脂异常、低白蛋白血症和高凝状态。据推测，外周血单核细胞中的Toll样受体（TLR）可能与INS疾病有关。感染似乎参与了INS的发病。本研究的目的是调查INS患者外周血单个核细胞（PBMC）中TLR的表达和功能，以及与两种人类内源性逆转录病毒（HERV）K和W表达的关系。
本研究纳入了37例初发且未经治疗的微小病变型肾病（MCD）患儿，MCD是肾病综合征（INS）最常见的单一形式，以及20名健康对照（HC）。采用ΔΔCt法对患者与正常样本中靶基因的表达进行相对定量。
在所有分析样本中均检测到HERV K和W的表达，但INS组的表达水平远低于HC组，HERV-K和-W的P值分别为<0.0001和0.0002。INS组中TLR2高表达的有10例，而HC组为17例（58.8%）；TLR3高表达的有3例，而HC组为17例（17.6%）；TLR4高表达的有12例，而HC组为17例（70.6%）；TLR9高表达的有9例，而HC组为17例（52.9%）（图2）。TLR2、3和4的不同表达具有统计学意义（P值分别为0.0183、0.0218和0.0034），TLR9则无统计学意义（P=0.2010）。统计分析表明，HERV-K和HERV-W的低表达与TLR的高表达之间存在显著相关性。考虑到所有TLR的表达与HERV表达的比较，我们得到了具有统计学意义的P<0.0001。
我们描述了由TLR介导的HERV-W和HERV-K的pol基因下调。
