儿童HSP血浆IFN-γ、IL-6、IL-17和TGF-β1水平对评价紫癜性肾炎的临床意义
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摘要
目的探讨儿童过敏性紫癜(HSP)血浆干扰素-γ(IFN-γ)、白细胞介素-6(IL-6)、白细胞介素-17(IL-17)、转化生长因子-β1(TGF-β1)表达水平在评价紫癜性肾炎(HSPN)中的临床意义。方法 HSP急性期患儿138例为研究对象,依据是否合并HSPN分为HSP组(n=94例)和HSPN组(n=44例),同期选择健康体检的儿童50例为对照组。检测3组受试儿童血浆炎性细胞因子IFN-γ、IL-6、IL-17、TGF-β1水平,采用多元Logistic回归分析此类炎性细胞因子表达水平与HSPN发生的关系,并绘制利用受试者工作特征(ROC)曲线评价其与HSPN发生的临床价值。结果 HSPN组血浆IFN-γ、IL-6、IL-17、TGF-β1表达水平高于HSP组,HSP组高于对照组(P<0.05),3组比较差异有统计学意义(P<0.05)。多元Logistic回归分析显示IFN-γ、IL-6、IL-17和TGF-β1与HSPN的发生呈独立正相关(OR分别为1.984,2.259,2.763和1.875,P<0.05)。ROC曲线分析显示IFN-γ、IL-6、IL-17和TGF-β1预测HSPN的曲线下面积(AUC)分别为0.728、0.814、0.869和0.656。敏感性分别为81.12%、80.62%、87.42%和73.81%,特异性分别为70.40%、83.27%、84.56%和72.71%,最佳界限值分别为12.60、18.16、74.38、6.97 pg/ml。结论 IFN-γ、IL-6、IL-17、TGF-β1表达水平增高可能参与了HSP及其HSPN的发病,与HSPN的发生呈正相关,可作为早期诊断和预测HSPN发生的有效指标,临床应当密切关注此类炎性细胞因子的变化以指导临床预后评估。
Objective To investigate the clinical significance of the expression levels of plasma interferon-γ(IFN-γ),interleukin-6(IL-6),interleukin-17(IL-17) and transforming growth factor-β1(TGF-β1) in evaluating nephritis in evaluating urpura nephritis in children with henoch-schonlein purpura(HSP).Methods A total of 138 children patients with acute HSO who were admitted and treated in our hospital from June 2015 to June 2015 were enrolled in the study,who were divided into HSP groups(n=94) and HSPN group(n=44) according to whether they had HSPN or not,at the same time,the other 50 healthy children who underwent physical examination were enrolled as control group.The expression levels of plasma inflammatory cytokines including IFN-γ,IL-6,IL-17 and TGF-β1 were detected.Moreover the correlation between these inflammatory cytokines and the pathogenesis of HSPN was analyzed by multivariate Logistic regression analysis,and the receiver-operating characteristic(ROC) curve was drawn to evaluate its clinical significance in diagnosis of HSPN.Results The expression levels of plasma IFN-γ,IL-6,IL-17 and TGF-β1 in HSPN group were significantly higher than those in HSP group,moreover,which in HSP group were significantly higher than those in control group(P<0.05),there were significant differences aming the three groups(P<0.05).Multivariate Logistic regression analysis showed that IFN-γ,IL-6,IL-17 and TGF-β1 were independent positive correlated with the incidence of HSPN(OR=1.984,1.984,2.763 and 1.875,respectively,P<0.05).ROC curve analysis showed that the area under curve(AUC) of IFN-γ,IL-6,IL-17 and TGF-β1 in predicting HSPN was 0.728,0.814,0.869 and 0.656,respectively,and the sensitivity was 81.12%,80.62%,87.42% and81.12% respectively,and specificity was 70.40%,83.27%,84.56% and 70.40%,respectively,the optimal threshold value was 12.60 pg/ml,18.16 pg/ml and 74.38 pg/ml and 6.97 pg/ml,respectively.Conclusion The increase of expression levels of IFN-γ,IL-6,IL-17 and TGF-β1 may be involved in the pathogenesis of HSP and HSPN,which is positively correlated with the incidence of HSPN,thus,which can be used as an early diagnosis and effective index to predict the incidence of HSPN,therefor,these indexes should be paid much attention to in clinical practice so as to guide clinical prognosis evaluation.
Objective To investigate the clinical significance of the expression levels of plasma interferon-γ(IFN-γ),interleukin-6(IL-6),interleukin-17(IL-17) and transforming growth factor-β1(TGF-β1) in evaluating nephritis in evaluating urpura nephritis in children with henoch-schonlein purpura(HSP).Methods A total of 138 children patients with acute HSO who were admitted and treated in our hospital from June 2015 to June 2015 were enrolled in the study,who were divided into HSP groups(n=94) and HSPN group(n=44) according to whether they had HSPN or not,at the same time,the other 50 healthy children who underwent physical examination were enrolled as control group.The expression levels of plasma inflammatory cytokines including IFN-γ,IL-6,IL-17 and TGF-β1 were detected.Moreover the correlation between these inflammatory cytokines and the pathogenesis of HSPN was analyzed by multivariate Logistic regression analysis,and the receiver-operating characteristic(ROC) curve was drawn to evaluate its clinical significance in diagnosis of HSPN.Results The expression levels of plasma IFN-γ,IL-6,IL-17 and TGF-β1 in HSPN group were significantly higher than those in HSP group,moreover,which in HSP group were significantly higher than those in control group(P<0.05),there were significant differences aming the three groups(P<0.05).Multivariate Logistic regression analysis showed that IFN-γ,IL-6,IL-17 and TGF-β1 were independent positive correlated with the incidence of HSPN(OR=1.984,1.984,2.763 and 1.875,respectively,P<0.05).ROC curve analysis showed that the area under curve(AUC) of IFN-γ,IL-6,IL-17 and TGF-β1 in predicting HSPN was 0.728,0.814,0.869 and 0.656,respectively,and the sensitivity was 81.12%,80.62%,87.42% and81.12% respectively,and specificity was 70.40%,83.27%,84.56% and 70.40%,respectively,the optimal threshold value was 12.60 pg/ml,18.16 pg/ml and 74.38 pg/ml and 6.97 pg/ml,respectively.Conclusion The increase of expression levels of IFN-γ,IL-6,IL-17 and TGF-β1 may be involved in the pathogenesis of HSP and HSPN,which is positively correlated with the incidence of HSPN,thus,which can be used as an early diagnosis and effective index to predict the incidence of HSPN,therefor,these indexes should be paid much attention to in clinical practice so as to guide clinical prognosis evaluation.
引文
1 Dan F,Huang WY,Sheng H,et al.A single-center analysis of HenochSchonlein purpura nephritis with nephrotic proteinuria in children.Pediatr Rheumatol Online J,2017,15:15-21.
2 Mao SJ,Huang XM.Tripterygium wilfordii Hook F is efficacious in the treatment of Henoch-Schonlein purpura nephritis in children.World Journal of Pediatrics,2016,12:375-376.
3刘玲,张东风,李春珍,等.儿童过敏性紫癜肾炎的临床及病理分析.临床儿科杂志,2015,33:151.
4 Ichiyama S,Matayoshi T,Kaneko T,et al.Successful multitarget therapy using prednisolone,mizoribine and tacrolimus for Henoch-Schonlein purpura nephritis in children.Journal of Dermatology,2016,44:e56-e57.
5李沫民,柳旎,张淼,等.过敏性紫癜患儿血清中期因子变化的临床意义.中国实验血液学杂志,2017,25:181-185.
6张玲.过敏性紫癜患儿外周血Th17细胞与Treg细胞失衡的研究.中国免疫学杂志,2015,23:1404-1406.
7 Mills JA,Michel BA,Bloch DA,et al.The American College of Rheumatology 1990 criteria for the classification of HenochSchonleinpurpura.Arthritis Rheum,1990,33:1114-1121.
8中华医学会儿科学分会肾脏学组.紫癜性肾炎诊治循证指南(2016).中华儿科杂志,2017,55:647-651.
9 Welcher AA,Boedigheimer M,Kivitz AJ,et al.Blockade of interferon-γnormalizes interferon-regulated gene expression and serum CXCL10 levels in patients with systemic lupus erythematosus.Arthritis&Rheumatology,2015,67:2713-2722.
10童科珍,毛建华,傅海东,等.肾病综合征患儿血清细胞因子水平及T细胞亚群变化的临床意义.中华临床免疫和变态反应杂志,2016,10:351-356.
11杨涛,张韬,陈华茜,等.肾康注射液联合贝那普利对慢性肾小球肾炎患者外周血IFN-γ,IL-4及IL-17水平的影响.现代生物医学进展,2017,17:2542-2545.
12 Ji M,Lu Y,Zhao C,et al.C5a Induces the synthesis of IL-6 and TNF-αin rat glomerular mesangial cells through MAPK signaling pathways.Plos One,2016,11:e0161867.
13 Lu M,Gao Y,Chen G,et al.Relationships of Urinary VEGF/CR and IL-6/CR with glomerular pathological injury in asymptomatic hematuria patients.Med Sci Monit,2015,21:356-362.
14 Xu H,Pan Y,Li W,et al.Association between IL17A and IL17Fpolymorphisms and risk of Henoch-Schonlein purpura in Chinese children.Rheumatology International,2016,36:829-835.
15王倩,胡金伟,马秀敏,等.Th17细胞与自身免疫性疾病关系的研究进展.现代免疫学,2015,31:524-526.
16 Azadegan-Dehkordi F,Bagheri N,Shirzad H,et al.The role of Th1 and Th17 cells in glomerulonephritis.J Nephropathol,2015,4:32-37.
17 Yuan Y,Yang M,Wang K,et al.Excessive activation of the TLR9/TGF-β1/PDGF-B pathway in the peripheral blood of patients with systemic lupus erythematosus.Arthritis Research&Therapy,2017,19:70.
18刘意,赵林双,林延艳,等.白细胞介素22介导转化生长因子-β1高表达与糖尿病肾纤维化相关性分析.中华内分泌代谢杂志,2017,33:769-775.
19贾会玉,李中南,陈光亮.糖尿病肾病中转化生长因子β-1/Sma和Mad相关蛋白信号通路的作用及其相关药物研究进展.中国药理学与毒理学杂志,2016,30:266-271.
20 Zhao S,Shen H,Gu W,et al.Evaluation of TGF-β1 and MCP-1expression and tubulointerstitial fibrosis in children with Henoch-Sch nlein purpura nephritis and Ig A nephropathy:A clinical correlation.Clinics,2017,72:95-101.
2 Mao SJ,Huang XM.Tripterygium wilfordii Hook F is efficacious in the treatment of Henoch-Schonlein purpura nephritis in children.World Journal of Pediatrics,2016,12:375-376.
3刘玲,张东风,李春珍,等.儿童过敏性紫癜肾炎的临床及病理分析.临床儿科杂志,2015,33:151.
4 Ichiyama S,Matayoshi T,Kaneko T,et al.Successful multitarget therapy using prednisolone,mizoribine and tacrolimus for Henoch-Schonlein purpura nephritis in children.Journal of Dermatology,2016,44:e56-e57.
5李沫民,柳旎,张淼,等.过敏性紫癜患儿血清中期因子变化的临床意义.中国实验血液学杂志,2017,25:181-185.
6张玲.过敏性紫癜患儿外周血Th17细胞与Treg细胞失衡的研究.中国免疫学杂志,2015,23:1404-1406.
7 Mills JA,Michel BA,Bloch DA,et al.The American College of Rheumatology 1990 criteria for the classification of HenochSchonleinpurpura.Arthritis Rheum,1990,33:1114-1121.
8中华医学会儿科学分会肾脏学组.紫癜性肾炎诊治循证指南(2016).中华儿科杂志,2017,55:647-651.
9 Welcher AA,Boedigheimer M,Kivitz AJ,et al.Blockade of interferon-γnormalizes interferon-regulated gene expression and serum CXCL10 levels in patients with systemic lupus erythematosus.Arthritis&Rheumatology,2015,67:2713-2722.
10童科珍,毛建华,傅海东,等.肾病综合征患儿血清细胞因子水平及T细胞亚群变化的临床意义.中华临床免疫和变态反应杂志,2016,10:351-356.
11杨涛,张韬,陈华茜,等.肾康注射液联合贝那普利对慢性肾小球肾炎患者外周血IFN-γ,IL-4及IL-17水平的影响.现代生物医学进展,2017,17:2542-2545.
12 Ji M,Lu Y,Zhao C,et al.C5a Induces the synthesis of IL-6 and TNF-αin rat glomerular mesangial cells through MAPK signaling pathways.Plos One,2016,11:e0161867.
13 Lu M,Gao Y,Chen G,et al.Relationships of Urinary VEGF/CR and IL-6/CR with glomerular pathological injury in asymptomatic hematuria patients.Med Sci Monit,2015,21:356-362.
14 Xu H,Pan Y,Li W,et al.Association between IL17A and IL17Fpolymorphisms and risk of Henoch-Schonlein purpura in Chinese children.Rheumatology International,2016,36:829-835.
15王倩,胡金伟,马秀敏,等.Th17细胞与自身免疫性疾病关系的研究进展.现代免疫学,2015,31:524-526.
16 Azadegan-Dehkordi F,Bagheri N,Shirzad H,et al.The role of Th1 and Th17 cells in glomerulonephritis.J Nephropathol,2015,4:32-37.
17 Yuan Y,Yang M,Wang K,et al.Excessive activation of the TLR9/TGF-β1/PDGF-B pathway in the peripheral blood of patients with systemic lupus erythematosus.Arthritis Research&Therapy,2017,19:70.
18刘意,赵林双,林延艳,等.白细胞介素22介导转化生长因子-β1高表达与糖尿病肾纤维化相关性分析.中华内分泌代谢杂志,2017,33:769-775.
19贾会玉,李中南,陈光亮.糖尿病肾病中转化生长因子β-1/Sma和Mad相关蛋白信号通路的作用及其相关药物研究进展.中国药理学与毒理学杂志,2016,30:266-271.
20 Zhao S,Shen H,Gu W,et al.Evaluation of TGF-β1 and MCP-1expression and tubulointerstitial fibrosis in children with Henoch-Sch nlein purpura nephritis and Ig A nephropathy:A clinical correlation.Clinics,2017,72:95-101.