系统性红斑狼疮患者血清miR-155水平变化及意义

Changes in levels of serum miR-155 in patients with systemic lupus erythematosus

目的探讨血清miR-155在系统性红斑狼疮(SLE)患者中的水平变化及意义。方法收集SLE患者50例(SLE组),健康对照人群40例(对照组),经糖皮质激素规律治疗的SLE患者45例(治疗组)。采用RT-PCR方法检测血清miR-155水平,并分析其水平与患者临床特征、疗效之间的关系及对SLE的诊断和预后价值。结果SLE组血清miR-155相对表达水平低于对照组(P<0.001)。SLE组中血清miR-155的表达水平与肾小球滤过率(r=0.576,P<0.001)、血清高敏C反应蛋白(hs-CRP)呈显著正相关(r=0.406,P=0.003),而与尿蛋白水平(r=-0.480,P=0.004)、狼疮活动指数(r=-0.553,P<0.001)呈显著负相关。对照组中血清miR-155与临床各指标无显著相关性(P均>0.05)。血清miR-155诊断SLE受试者特征(ROC)曲线的曲线下面积为0.867,诊断的灵敏度和特异度分别为84%和78%,其曲线下面积显著高于血清补体C4和hs-CRP(P均<0.01);miR-155预测SLE患者糖皮质激素治疗疗效的ROC曲线的曲线下面积为0.782,灵敏度和特异度分别为78%、72%。疗效好(狼疮活动评分较治疗前减少3分以上)组患者治疗前血清miR-155表达水平显著高于疗效差(狼疮活动评分较治疗前减少小于3分或者没有减少)组(P<0.05)。疗效好组治疗前后血清miR-155水平比较,P<0.05,而疗效差组治疗前后比较,P>0.05。高表达miR-155组的疗效好患者所占比例显著高于低表达组(χ2=2.29,P<0.05)。高表达miR-155组从治疗后到出现疾病复发的平均时间显著长于低表达miR-155组(46比29个月,P=0.002)。结论 SLE患者血清miR-155水平升高。miR-155是潜在诊断指标、治疗靶点和预后因子。

Objective To investigate the changes in levels of serum miR-155 in patients with systemic lupus erythematosus（ SLE） and its significance. Methods Serum samples were collected from 50 patients with SLE（ SLE group）,and 40 healthy individuals（ control group） and 45 SLE patients receiving glucocorticoids treatment（ treatment group） were also selected. The serum level of miR-155 was detected by RT-q PCR. Then,the association between serum miR-155 level and clinical characteristics,treatment response of glucocorticoids was analyzed. Moreover,the diagnostic and prognostic value of serum miR-155 in SLE patients receiving glucocorticoid treatment was also investigated. Results In the SLE group,the serum miR-155 level was positively correlated with GFR（ r = 0. 576,P〈0. 001） and hs-CRP（ r = 0. 406,P =0. 003） levels,while was negatively correlated with proteinuria（ r =-0. 480,P = 0. 004） and SLEDAI（ r =-0. 553,P〈0. 001）. However,in the control group,no significant correlation was found between miR-155 and those four indexes.Receiver operator curve analysis showed that the area under the curve（ AUC） of miR-155 was 0. 867,which was significantly higher than C4 and hs-CRP（ z = 3. 837,P〈0. 01）. Besides,the sensitivity and specificity of miR-155 reached84% and 78%,respectively. Moreover,the AUC of miR-155 in differentiating response to glucocorticoids was 0. 782,with the sensitivity and specificity of 78% and 72%,respectively. The expression of miR-155 was significantly increased in patients showing better response to glucocorticoids treatment（ the SLEDAI decreased more than 3 points after treatment） as compared with that of patients showing poor response（ the SLEDAI decreased no more than 3 points after treatment）（ P〈0. 05）. Then we compared the expression variety of miR-155 in SLE patients before and after the glucocorticoids treatment.Our results showed that a statistical significance was found in patients with better response（ P〈0. 05）,while no statistical significance was found in patients with poor response（ P〉0. 05）. The proportion of patients showing better response to glucocorticoid was significantly higher in the high miR-155 expression group than in the low expression group（ χ2= 2. 29,P〈0. 05）. More importantly,SLE patients with high miR-155 expression showed longer disease-free survival as compared with that of patients with low miR-155 expression（ 46 months vs. 29 months,P = 0. 002）. Conclusion Serum miR-155 is highly expressed in patients with SLE,and can serve as a potential diagnostic marker,therapeutic target and prognostic indicator in SLE.