The Clinical Significance And The Expression Of MiR-146a,miR-155,Ets-1 Gene And IRAK1 Gene In PBMCs Of RA Patients

Objective:To detect the expression of microRNA-146a(miR-146a),microRNA-155(miR-155),Ets-1 gene,IL-1 receptor-associated kinase 1(IRAK1)gene of the peripheral mononuclear cells(PBMCs)and the inflammatory factors of plasma in RA patients and explore the relationship between the expression levels and the disease activity,their efforts on the pathogenesis of RA were explored.Methods:44 RA patients were obtained from the department of Traditional Chinese Rheumatology of Nanfang hospital from September 2015 to May 2016,including 6 males and 38 females patients,according to RA patients cohort,including high active 23 RA cases,4 males and 19 females;including low active 21 RA cases,2 males and 19 females.All RA patients satisfy the 2010 American College of Rheumatology/European league Against Rheumatism Classification criteria.Healthy controls include 6 males and 16 females,none of cases with other autoimmune diseases or severe heart,kidney and liver diseases.The levels of miR-146a,miR-155,Ets-1,IRAK1 were measured using real-time polymerase chain reaction(RT-PCR),ELISA was used to detect the protein levels of Ets-1 and IRAKI in plasma,The levels of TNF-a,IL-1?,IL-2,IL-6,IL-17 and IL-21 in plasma were detected by ELISA,the correlation of them with the clinical indicators of RA patients were analyzed.Non-parametric test,t test,One-way ANOVA,pearson and spearman correlation analysis were used for statistical analysis.Results:The relative expression levels of miR-146a,miR-155 were higher in PBMCs of RA patients than in normal control group(P<0.05).The expression of miR-146a was significantly higher in active RA patients group than that in low disease activity group(P<0.05).There was no difference between the low disease activity group and normal control group(P>0.05).There was no significant difference in the relative expression level of Ets-1 between the RA group and normal control group(P<0.05),but Ets-lwas lower in active RA patients group than that in low disease activity group and normal control group(P<0.05),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 PBMCs was significantly lower in the high disease activity group and low disease activity group(P<0.05).However,there was no difference the high activity group and low disease activity group(P>0.05).The expression levels of Ets-1 and IRAK1 in RA plasma were not significantly different from those in normal controls.TNF-?,IL-1?,IL-6 and IL-21 levels were increased in RA patients.There was no significant difference in IL-2 and IL-17 between RA patients and healthy controls.The expression level of miR-155 was positively correlated to ESR,and negatively with Hb(r=0.318,P=0.021;r=-0.386,P=0.008).The expression levels of Ets-1 was negatively correlated to CRP(r=-0.408,P=0.007)..The expression levels of IRAK1 were negatively correlated to RF,DAS28,total complement(r=-0.513,P=0.001;r=-0.332,P =0.029;r=-0.49,P=0.015).Conclusion:The expression of miR-146a and miR-155 expression levels were up-regulated and the expression levels of Ets-1 and IRAK1 expression levels were down-regulated in patients with RA,they may involve the pathogenesis of RA.Considering the limitation of sample size in this study,future study with large sample size is needed to confirm the relationship between miR-146a,miR-155,and Ets-1,IRAKI.Furthermore,the studies focused on the related mechanism of these molecules in RA are worthy to be done.