血清中期因子在儿童过敏性紫癜及紫癜性肾炎的变化及意义

Changes and significance of serum midkine in children with allergic purpura and purpura nephritis

目的 通过检测儿童过敏性紫癜( Henoch-Schonlein purpura, HSP)及紫癜性肾炎(Henoch-Schonlein purpura nephritis,HSPN)患者血清内中期因子(midkine,MK)水平,研究MK在HSP、HSPN发病机制中的作用.方法 选取2016年12月至2018年1月中国医科大学附属盛京医院小儿肾脏风湿免疫内科收治的35例确诊病例作为病例组,其中HSP组10例,HSPN组25例.又将HSPN组根据24 h尿蛋白定量水平分为非肾病水平蛋白尿组10例,肾病水平蛋白尿组15例.健康对照组为同期于我院发育儿科门诊健康体检的健康儿童12名.患儿确诊后采集血样检测MK.收集肾功能、24 h尿蛋白定量、免疫球蛋白等指标.比较各组间血清MK、肾功能指标等的差异,分析MK与各临床指标之间的相关性,采用受试者工作特征(ROC)曲线分析MK诊断HSP、HSPN的价值.结果 病例组血清MK水平明显高于健康对照组[(289. 34 ± 160. 70) pg/ml比 (100. 03 ± 56. 75) pg/ml)],差异有统计学意义(P<0. 05);且MK浓度在HSPN(肾病水平蛋白尿)组、HSPN(非肾病水平蛋白尿)组、HSP组间比较差异仍具有统计学意义[(449. 91 ± 141. 91) pg/ml比(244. 04 ± 89. 15) pg/ml 比 (175. 94 ± 46. 30) pg/ml)](P<0. 05).在病例组中,MK与尿微量白蛋白(r=0. 54)、IgA( r=0. 132)、IgE( r=0. 304)、血β2微球蛋白(r=0. 483)、24 h尿蛋白定量/体重(r=0. 503)、尿转铁蛋白水平(r=0. 509)呈正相关(P<0. 05).根据ROC曲线,MK诊断HSP的曲线下面积值为0. 908(95%CI 0. 828-0. 988),诊断HSP的最佳值为182. 762 pg/ml,敏感性、特异性分别为81. 4%、91. 7%;MK诊断HSPN的曲线下面积值为0. 947 (95%CI 0. 888-1. 000),预测诊断 HSPN 的最佳值为218. 186 pg/ml,敏感性、特异性分别为84. 0%、95. 5%.结论 MK可能参与HSP、HSPN的发病过程,推测可为HSP及HSPN的临床诊断提供依据,并且在评估HSPN肾损害程度方面具有一定意义.

Objective To investigate the role of midkine(MK)in the pathogenesis of Henoch-Schonlein purpura(HSP)and Henoch-Schonlein purpura nephritis(HSPN).Methods In the case group,35 cases were hospitalized in the pediatric kidney rheumatism immunology ward of Shengjing hospital affiliated to China Medical University from December 2016 to January 2018.Among them,10 cases were HSP,25 were HSPN.According to quantitative level of 24-hour urine protein,HSPN group was divided into HSPN(nephrotic level of proteinuria)group of 15 cases and HSPN(non-nephrotic level of proteinuria)group of 10 cases.The control group consisted of 12 healthy cases who underwent physical examination at outpatient department in the same period in the developmental pediatric clinic of our hospital.Blood samples were collected to detect MK.The other clinical datas including renal function,24-hour urine protein quantitative,immunoglobulin,etc were collected.The serum MK and renal function indexes were compared among groups.The correlation between MK and various clinical indicators was analyzed,and the receiver operating characteristic(ROC)curve was used to analyze the diagnostic significance of MK for HSP and HSPN.Results MK level of case group was higher than that of healthy control group[(289.34±160.70)pg/ml vs.(100.03±56.75)pg/ml,P<0.05].Moreover,the difference of MK concentration among the HSPN(nephrotic proteinuria)group,the HSPN(non-nephrotic proteinuria)group and the HSP group was still statistically significant[(449.91±141.91)pg/ml vs.(244.04±89.15)pg/ml vs.(175.94±46.30)pg/ml,P<0.05].MK was positively correlated with urine microalbumin(r=0.54),IgA(r=0.132),IgE(r=0.304),urineβ2 microglobulin(r=0.483),24-hour urine protein/body weight(r=0.503),and urine transferrin level(r=0.509)in the case group(P<0.05).According to the ROC curve,the area under ROC of MK for predicting the diagnosis of HSP was 0.908(95%CI 0.828-0.988).The optimal value in predicting the diagnosis of HSP was 182.762 pg/ml,with sensitivity and specificity of 81.4%and 91.7%.The area under ROC of MK in predicting HSPN was 0.947(95%CI 0.888-1.000),and the optimal value of predicting HSPN was 218.186 pg/ml,with sensitivity and specificity of 84.0%and 95.5%.Conclusion MK may be involved in the pathogenesis of HSP and HSPN.It can provide the basis for clinical diagnosis of HSP and HSPN,and has significance in evaluating the degree of renal damage of HSPN.