MicroRNA-22和microRNA-1825在幼年系统性红斑狼疮诊断和鉴别诊断中的作用

Role of microRNA - 22 and microRNA - 1825 in the diagnosis and differential diagnosis of juvenile systemic lupus erythematous

目的探索microRNA（miR）-22和miR-1825在幼年系统性红斑狼疮（JSLE）诊断及鉴别诊断中的应用价值。方法选取2013年6月至2014年5月首都儿科研究所附属儿童医院收治的JSLE患儿为研究组，选取同期收治的全身型幼年特发性关节炎（sJIA）、肾病综合征（Ns）、川崎病（KD）、过敏性紫癜（HSP）患儿为病例对照组，选取健康体检儿童为健康对照组。采用实时荧光定量-PCR方法检测研究组患者、病例对照组患者和健康对照组儿童血浆中miR-22和miR-1825表达水平，分析3组间miR-22和miR-1825表达水平的差异。受试者工作特征曲线（ROC曲线）评价miR-22和miR-1825作为诊断指标的灵敏度和特异度。用Targetscan、PicTar、miranda3个数据库预测miR-22和miR-1825靶基因，使用基因本体（GO）分析预测靶基因的分子功能、参与的生物学过程，京都基因与基因组百科全书通路（KEGG通路）分析预测靶基因参与的相关免疫学通路。结果研究组JSLE患儿血浆miR-22和miR-1825表达水平均低于健康儿童，差异均有统计学意义（t=-3．076、-9．054，P〈0．01、0．0001），亦低于病例对照组sJIA、NS、KD、HSP患儿表达水平（t=-4．410、-4．477、-4．494、-2．971，P均〈0．0001；t=-9．043、-6．045、-10．416、-8．712，P均〈0．0001），病例对照组患儿血浆miR-22和miR-1825miRNA的表达水平与健康对照组儿童比较差异均无统计学意义（P均〉0．05）。miR-22健康对照组和研究组ROC曲线下面积为0．777，miR-1825健康对照组和研究组ROC曲线下面积为1．000。miR-22：JSLE患儿与sJIA、NS、KD、HSP患儿ROC曲线下面积为0．731～1．000；miR-1825：JSLE患儿与sJIA、NS、KD、HSP患儿ROC曲线下面积为0．939～1．000。JSLE患儿外周血miR-22的表达水平与补体C3具有相关性（r=0．493，P=0．027）。结论血浆中miR-22和miR-1825表达水平对JSLE的诊断和鉴别诊断具有-定参考价值，miR-22可在一定程度上反映疾病活动性。

Objective To explore the role of microRNA （miR） -22 and miR - 1825 in the diagnosis and differential diagnosis of juvenile systemic lupus erythematous （JSLE）. Methods The cases of JSLE hospitalized in Capital Institute of Pediatrics Teaching Hospital Affiliated to Peking University from June 2013 to May 2014 were se- lected as study group. The cases with systemic juvenile idiopathic arthritis （sJIA） , nephrotie syndrome （ NS）, Kawasaki disease （KD） , Henoch -Schonlein purpura（HSP） were selected as patients control group. The healthy children were se- lected as healthy control group. The expression levels of miR - 22 and miR - 1825 in the plasma of JSLE, sJIA, NS, KD, HSP and healthy children were detected by using real - time PCR respectively. Receiver operating characteristic curve （ ROC ） analysis was performed to evaluate the value of miR -22 and miR - 1825 miRNA as a biomarker with the sensitivity and specificity. Three data bases,included Targetsean, PicTar and miranda, were applied to predict the target gene. The target gene was analyzed by adopting Gene Ontology （GO） in terms of molecular function, biological process and cellular component, and by adopting Kyoto Encyclopedia of Genes and Genomes （ KEGG ） in terms of pathway. Results Compared with healthy children, the amount of miR -22 and miR - 1825 in JSLE patients were lower, and there were significant differences（ t = - 3. 076, - 9. 054 ,P 〈 0.01,0. 000 1 ）. The levels of the miR - 22 and miR - 1825 miRNAs in controls of sJIA,NS,KD,HSP were significantly higher than those of JSLE （t = - 4. 410, - 4. 477, -4. 494, -2. 971,all P 〈0. 000 1 ;t = -9. 043, -6. 045, - 10. 416, - 8. 712, all P 〈0. 000 l） ,but there was no difference compared with healthy children （ all P 〉 0.05 ）. The area under ROC curve （ AUC ） of miR - 22 between JSLE and healthy children was 0. 777. The AUC of miR - 1825 between JSLE and healthy children was 1. 000. The AUCs be- tween JSLE and controls of sJIA, NS, KD, HSP of miR - 22 were 0.731 - 1. 000. The AUCs between JSLE and controls of sJIA,NS,KD ,HSP of miR- 1825 were 0. 939 -1. 000. There was positive relation between the amount of miR- 22 and complement C3 in plasma（ r = 0. 493, P = 0. 027 ）. Conclusions The amount of miR - 22 and miR - 1825 in theplasma of JSLE embrace the potential of distinguishing JSLE from healthy children, sJIA, NS, KD, HSP. MiR - 22 has the ability to predict the activity of JSLE.