类风湿关节炎患者外周血miR-146a、miR-155、Ets-1以及IRAK1的表达及临床意义

Expression and clinical significance of miR-146a,miR-155,Ets-1 and IRAK1 in the peripheral blood mononuclear cells of patients with rheumatoid arthritis

为探讨类风湿关节炎(rheumatoid arthritis,RA)患者PBMC中miR-146a、miR-155、Ets-1和IRAK1的表达水平及与病情活动度的相关性,收集RA高活动期患者23例、低活动期患者21例和健康志愿者22例,采用qRT-PCR检测PBMC中miR-146a、miR-155、Ets-1、IRAK1的相对表达水平,同时分析其与临床及实验室指标的相关性。RA患者PBMC的miR-146a、miR-155相对表达量显著高于健康对照组(P<0.05),高活动组高于低活动组(P<0.05)、低活动组与健康对照组差异无统计学意义(P>0.05);RA患者PBMC的Ets-1表达水平与健康对照组差异无统计学意义,高活动组显著低于低活动组和健康对照组(P<0.05)、低活动组与健康对照组差异无统计学意义(P>0.05);RA患者PBMC的IRAK1表达水平显著低于健康对照组(P<0.05),高活动组显著低于健康对照组(P<0.01)、低活动组显著低于健康对照组(P<0.05),而高活动组与低活动组间无统计学差异(P>0.05)。在RA患者中miR-155表达水平与血沉正相关(r=0.319,P=0.042)而与血红蛋白负相关(r=-0.386,P=0.017);Ets-1与CRP负相关(r=-0.408,P=0.007);IRAK1与RF、DAS 28、总补体负相关(r=-0.513,P=0.001;r=-0.332,P=0.029;r=-0.49,P=0.015)。研究结果显示,RA高活动组患者PBMC中miR-146a、miR-155表达升高,Ets-1、IRAK1表达降低,可能参与了RA发病过程的调控;但本研究样本量有限,miR-146a、miR-155和Ets-1、IRAK1参与RA发病的关系有待后续大样本研究证实,且相关调控机制仍需进一步深入研究。

This study aimed to investigate the expression of miR-146a, miR-155, Ets-1 and IRAK1 in the peripheral blood mononuclear celI（PBMC） of patients with rheumatoid arthritis（RA） and their correlation with the disease activity. PBMC were separated from 44 RA patients and 22 healthy individuals. The levels of miR 146a, miR-155, Ets-1 and IRAK1 were measured using quantitative real-time polymerase chain reaction （qRT-PCR）, and their correlation with the clinical and laboratory param- eters of RA were analyzed. The relative expression levels of miR-146a, miR-155 were higher in PBMC of RA patients than in normal control group（P〈0.05） ,and were significantly higher in the active RA patients group than in the low disease activity group（P〈0.05）. There was no difference in the levels of miR-146a and miR-155 between the low disease activity group and normal control group（P〉0.05）. There was no significant difference in expression level of Ets-1 between the patient group and normal control group（P〈0.05） in a comprehensive （total） comparison. However, the expression level of Ets-1 was lower in high disease activity group than that in the low disease activity group and normal control group（P〈0.05）, while there was no difference between the low disease activity group and normal control group （P〉0.05）. Compared to the control group, the expression of IRAK1 in PBMC was significantly lower in the high disease activity group and low disease activity group （P〈 0.05）. However, there was no difference between the two activity groups （P〉0.05）. The expression levels of miR-155 was positively correlated to ESR（ r= 0. 319, P= 0. 042）, and negatively correlated to H b（ r= -0. 386, P= 0. 017）. The expression levels of Ets-1 were negatively correlated to CRP（r= -0. 408, P= 0. 007）. The expression levels of IRAK1 were negatively correlated to RF, DAS 28, total complement （r=-0. 513, P=0. 001; r=-0. 332, P =0. 029; r=-0. 490, P=0. 015）. In conclusion, the expression levels of miR-146a and miR-155 were up-regulated and the expression levels of Ets-1 and IRAK1 were down-regulated in patients with RA with high disease activity. Considering the limitation of sample size in this study, future study with larger sample size is needed to confirm the relationship between miR-146a, miR 155, Ets-1, IRAK1 and RA. Furthermore, studies focusing on the related mechanisms of these molecules in RA are worth to be done.