系统性红斑狼疮患者外周血单个核细胞miR-125b及miR-145的表达及临床意义

The expression and clinical significance of miR-125b and miR-145 in peripheral blood mononuclear cells of patients with systemic lupus erythematosus

目的探讨miR-125b及miR-145在系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMC)中的表达水平及其临床意义。方法选取海南省人民医院收治的136例SLE患者,采用SLE病情活动指数(SLEDAI)评分将其分为低活动组(n=75)和高活动组(n=61),另选取60例健康体检者作为对照组。采用实时定量PCR(RT-PCR)法检测各组PBMC中miR-125b及miR-145水平,分析其对SLE患者的诊断价值。Pearson相关分析SLE患者miR-125b及miR-145水平与抗双链DNA(dsDNA)抗体、C3、C4、IgG、血沉(ESR)、C反应蛋白(CRP)及SLEDAI评分的相关性。结果 SLE组、高活动组和低活动组抗dsDNA抗体、ESR、IgG及CRP水平均明显高于对照组(P<0.05),而C3及C4水平均明显低于对照组(P<0.05)。SLE组、高活动组和低活动组PBMC中miR-125b(0.84±0.23、0.42±0.09和1.53±0.28 vs 6.12±1.83)及miR-145(0.68±0.17、0.35±0.06和1.12±0.20 vs 2.15±0.64)表达水平均明显低于对照组(P<0.01),且高活动组PBMC中miR-125b(0.42±0.09 vs 1.53±0.28)及miR-145(0.35±0.06 vs1.12±0.20)表达水平明显低于低活动组(P<0.01)。SLE患者治疗后miR-125b(2.60±0.71 vs 0.84±0.23)及miR-145(1.96±0.58 vs 0.68±0.17)表达水平明显高于治疗前(P<0.01),SLE患者治疗后抗dsDNA抗体(96.24±17.20 vs 272.36±64.35)水平明显低于治疗前(P<0.01)。ROC曲线分析显示,miR-125b、miR-145及抗dsDNA抗体三项联合诊断SLE的AUC(95%CI)为0.928(0.871～0.986),其敏感度(90.4%)和特异度(85.0%)较好。相关分析显示,SLE患者miR-125b、miR-145与抗dsDNA抗体、IgG、SLEDAI评分均呈负相关(P<0.05),miR-125b与miR-145呈明显正相关(r=0.805,P<0.05)。结论 miR-125b及miR-145水平在SLE患者PBMC中明显降低,且与SLE病情活动相关,联合抗dsDNA抗体检测对SLE诊断具有一定价值。

To investigate the expression and clinical significance of miR-125b and miR-145 in peripheral blood mononuclear cells (PBMC)of patients with systemic lupus erythematosus (SLE),total of 136 SLE patients treated in Hainan Provincial People's Hospital were recruited and divided into low activity group (n=75)and high activity group (n=61)by SLE disease activity index (SLEDAI),and 60healthy persons were selected as control group.Real time quantitative PCR (RT-PCR)was used to detect the levels of miR-125b and miR-145 in PBMC of each group,and their diagnostic value for SLE patients was analyzed.Pearson correlation analysis was carried out for the association of miR-125b or miR-145 levels to anti double chain DNA (dsDNA)antibodies,C3,C4,IgG, erythrocyte sedimentation (ESR),C reactive protein (CRP)or SLEDAI scores in patients with SLE.Data showed that the anti dsDNA antibody,ESR,IgG and CRP levels in the SLE group,including the high activity group and the low activity group,were significantly higher than those in the control group (P<0.05),while the C3and C4levels were significantly lower than those in the control group (P<0.05).The expression levels of miR-125b and miR-145 in PBMC of SLE high activity group and low activity group were significantly lower than those in control group (P<0.01),and the expression levels of miR-125b and miR-145 in PBMC of high activity group were significantly lower than those in low activity group (P<0.01). After treatment,the expression of miR-125b and miR-145in patients with SLE were significantly increased (P< 0.01),while the level of anti dsDNA antibody decreased (P<0.01).The ROC curve analysis showed that the AUC (95%CI)of miR-125b,miR-145and anti dsDNA antibody joint diagnosis for SLE was 0.928,with sensitivity of 90.4%and specificity of 85%.The correlation analysis showed that miR-125b and miR-145in SLE patients were negatively correlated with anti dsDNA antibody,IgG and SLEDAI scores (P<0.05),while miR-125b and miR-145 were positively correlated (r=0.805,P<0.05).Taken together,the levels of miR-125b and miR-145in SLE patients are significantly lower,and associates with SLE disease activity.Combining detection of miR-125b,miR-145and anti-dsDNA antibodies may be valuable for SLE diagnosis.