Mishra Om P, Kumar Ravindra, Narayan Gopeshwar, Srivastava Pradeep, Abhinay Abhishek, Prasad Rajniti, Singh Ankur, Batra Vineeta V
Division of Pediatric Nephrology, Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi, India.
Pediatr Nephrol. 2017 Aug;32(8):1355-1361. doi: 10.1007/s00467-017-3613-8. Epub 2017 Feb 16.
The aims of this study were (1) to detect toll-like receptor (TLR)-3, TLR-4 and CD80 expression in peripheral blood mononuclear cells (PBMCs) and estimate urinary CD80 levels in children with idiopathic nephrotic syndrome and (2) to investigate the utility of these markers to differentiate between biopsy-proven minimal change disease (MCD) and focal segmental glomeruloscelerosis (FSGS).
The study included 70 patients with idiopathic nephrotic syndrome (NS), of whom 40 had steroid-sensitive NS (SSNS; 25 with active NS, 15 in remission) and 30 had steroid-resistant NS (SRNS) patients, and 23 healthy controls. TLR-3, TLR- 4 and CD80 mRNA expression levels in PBMCs were determined and the urinary CD80 level estimated.
Median TLR-3, TLR-4 and CD80 mRNA expression levels were higher in patients with active SSNS than in those with SRNS, and the latter patient group also had significantly lower expression levels than the controls. The expression levels of these markers were associated with reductions in remission. Patients with biopsy-proven MCD had higher median expression levels of these markers than those with FSGS, but the differences were not statistically significant. Median urinary CD80/creatinine values were significantly higher in patients with SSNS and SRNS than in the controls and steroid-sensitive patients in remission (p < 0.001). CD80 levels were also significantly higher in patients with MCD than in those with FSGS (p = 0.002). A cut-off level of >914.5 ng/g had a sensitivity of 86.6%, specificity 71.4% and area under the curve of 0.828 (95% confidence interval 0.678-0.978, p = 0.002) for the diagnosis of MCD.
Increased expressions of TLR-3, TLR-4 and CD80 mRNA and the level of urinary CD80/creatinine could be useful markers to differentiate patients of SSNS in relapse from those with SRNS. Further these markers can also distinguish biopsy proven MCD from FSGS in SRNS patients.
本研究的目的是：（1）检测特发性肾病综合征患儿外周血单个核细胞（PBMC）中Toll样受体（TLR）-3、TLR-4和CD80的表达，并评估尿CD80水平；（2）研究这些标志物在经活检证实的微小病变病（MCD）和局灶节段性肾小球硬化（FSGS）鉴别诊断中的作用。
本研究纳入70例特发性肾病综合征（NS）患者，其中40例为激素敏感型NS（SSNS；25例为活动期NS，15例为缓解期），30例为激素抵抗型NS（SRNS）患者，以及23例健康对照。测定PBMC中TLR-3、TLR-4和CD80 mRNA表达水平，并评估尿CD80水平。
活动期SSNS患者的TLR-3、TLR-4和CD80 mRNA表达水平中位数高于SRNS患者，且后者的表达水平也显著低于对照组。这些标志物的表达水平与缓解期的降低有关。经活检证实为MCD的患者这些标志物的表达水平中位数高于FSGS患者，但差异无统计学意义。SSNS和SRNS患者的尿CD80/肌酐值中位数显著高于对照组和缓解期的激素敏感患者（p<0.001）。MCD患者的CD80水平也显著高于FSGS患者（p=0.002）。诊断MCD时，>914.5 ng/g的截断水平敏感性为86.6%，特异性为71.4%，曲线下面积为0.828（95%置信区间0.678-0.978，p=0.002）。
TLR-3、TLR-4和CD80 mRNA表达增加以及尿CD80/肌酐水平可能是区分复发的SSNS患者和SRNS患者的有用标志物。此外，这些标志物还可以在SRNS患者中区分经活检证实的MCD和FSGS。
