尿NGAL、CXCL-16及HMGB1在儿童狼疮性肾炎中的表达水平及其诊断价值

Expression of urinary NGAL, CXCL-16 and HMGB1 in children with lupus nephritis and its diagnostic value

目的探讨尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、CXC趋化因子配体-16(CXCL-16)及高迁移率族蛋白B1(HMGB1)在儿童狼疮性肾炎(LN)中的表达水平及其诊断价值。方法选取2016年1月-2018年12月三亚中心医院收治的LN患儿95例,其中Ⅱ型16例、Ⅲ型19例、Ⅳ型38例、Ⅴ型18例、Ⅵ型4例,另选取健康体检正常者40名作为对照组。根据儿童系统性红斑狼疮病情活动指数(SLEDAI)评分将95例LN患儿分为LN稳定组(n=34,SLEDAI评分<10分),LN活动组(n=61,SLEDAI评分≥10分),酶联免疫吸附法测定各组尿NGAL、CXCL-16及HMGB1水平。ROC曲线分析尿NGAL、CXCL-16及HMGB1水平对儿童LN的诊断价值,Pearson相关分析LN患儿尿NGAL、CXCL-16及HMGB1水平与实验室指标的相关性。结果LN组尿NGAL、CXCL-16、HMGB1、抗dsDNA抗体、C反应蛋白(CRP)、血肌酐(SCr)及血尿素氮(BUN)水平均明显高于对照组,补体C3、补体C4及血清白蛋白(ALB)水平均明显低于对照组,差异均有统计学意义(P<0.05)。LN活动组尿NGAL、CXCL-16及HMGB1水平均明显高于LN稳定组(P<0.05)。不同分型LN患儿尿NGAL、CXCL-16及HMGB1水平均明显高于对照组(P<0.05),且Ⅴ~Ⅵ型和Ⅳ型尿NGAL、CXCL-16及HMGB1水平均明显高于Ⅱ~Ⅲ型(P<0.05)。ROC曲线分析显示,尿NGAL、CXCL-16及HMGB1水平三项联合诊断儿童LN的曲线下面积(0.91,95%CI:0.85~0.97)最大,其敏感度和特异度为91.50%和84.70%。相关分析显示,LN患儿尿NGAL、CXCL-16及HMGB1水平与SLEDAI评分、抗dsDNA抗体、SCr及BUN水平均呈正相关(P<0.05)。结论LN患儿尿NGAL、CXCL-16及HMGB1水平明显升高,且与LN活动度及病理分型相关,三项联合检测对儿童LN诊断具有较高的价值。

Objective To investigate the expression and diagnostic value of urinary neutrophil gelatinase associated lipid delivery protein(NGAL),CXC chemokine ligand-16(CXCL-16)and high mobility group protein B1(HMGB1)in children with lupus nephritis(LN).Methods From January 2016 to December 2018,95 children with LN were enrolled in our hospital,including 16 cases of typeⅡ,19 cases of typeⅢ,38 cases of typeⅣ,18 cases of typeⅤ,4 cases of typeⅥ,and 40 cases of normal physical examination as control group.The 95 children with LN were divided into LN stable group(n=34,SLEDAI score<10),LN active group(n=61,SLEDAI score≥10)with systemic lupus erythematosus(SLE)activity index(SLEDAI)score.The levels of urine NGAL,CXCL-16 and HMGB1 were measured by enzyme-linked immunosorbent assay.ROC curve were used to analyze the diagnostic value of urinary NGAL,CXCL-16 and HMGB1 levels in children with LN.Pearson correlation analysis was used to analyze the correlation between urinary NGAL,CXCL-16 and HMGB1 levels in children with LN and laboratory indicators.Results The levels of NGAL,CXCL-16,HMGB1,anti dsDNA antibody,C-reactive protein(CRP),serum creatinine(SCr)and blood urea nitrogen(BUN)in LN group were significantly higher than those in the control group(P<0.05),while the levels of C3,C4 and albumin(ALB)in LN group were significantly lower than those in the control group(P<0.05).The levels of NGAL,CXCL-16 and HMGB1 in LN active group were significantly higher than those in LN stable group(P<0.05).The levels of urine NGAL,CXCL-16 and HMGB1 in children with LN of different types were significantly higher than those of the control group(P<0.05),and the levels of NGAL,CXCL-16 and HMGB1 in the urine ofⅤ-ⅥandⅣwere significantly higher than those ofⅡ-Ⅲ(P<0.05).ROC curve analysis showed that the area under the curve(0.91,95%CI:0.85-0.97)of the combined diagnosis of urinary NGAL,CXCL-16 and HMGB1 levels was the largest,with sensitivity and specificity of 91.50%and 84.70%,respectively.Correlation analysis showed that urinary NGAL,CXCL-16 and HMGB1 levels were positively correlated with SLEDAI score,anti dsDNA antibody,SCr and BUN levels(P<0.05).Conclusions The levels of urine NGAL,CXCL-16 and HMGB1 in children with LN were significantly increased,and were related to LN activity and pathological classification.The three combined tests had a high value in the diagnosis of children with LN.