| Background:Rheumatoid arthritis(RA)is a chronic,multisystem autoimmune disease,which is mainly characterized by abnormal proliferation of synovial fibroblasts,infiltration of inflammatory cells,abnormal secretion of inflammatory cytokines,thickening of synovium and progressive destruction of articular cartilage and bone.In recent years,it has been found that pin1(peptide-prolyl cis-trans isomerase nima-interacting 1)can participate in the pathogenesis of autoimmune diseases,and it can activate cell signaling pathway,activate various immune cells and promote the release of cytokines.The latest research found that all-transretinoic acid(ATRA),as an inhibitor of Pin1,can regulate the expression of inflammatory factors by inhibiting Pin1,and can also regulate the differentiation of T-helper 17 cells(Thl7)and Regulatory T cell(Treg),thus maintaining the function and stability of Treg under inflammatory conditions.This provides a new basis for the diagnosis of RA and a new idea for the treatment of RA.Objective:1.to explore the expression of Pin1 activity in periphe RAl blood of ra patients and the value and significance of Th17/Treg cells;2.To explore the correlation between Pin1 in peripheral blood of RA patients and disease activity index,Th17/Treg and cytokines;3.To analyze the effect of ATRA on Pin1 and Th17/Treg in peripheral blood of RA patients.Methods:1.100 RA patients and 20 healthy controls were collected(the healthy controls were from the same period of physical examination in our hospital).The collected 100 RA patients all met the classification standard of RA by ACR/EULAR in 2010,and excluded those complicated with other autoimmune diseases and those with cancer,tuberculosis and severe infection.According to whether or not to use drugs,they were divided into two groups: RA initial treatment group(50 cases)and RA medication group(50 cases),and the RA medication group was further divided into two groups: A.Traditional treatment group(29 cases)and Retinoic acid treatment group(21 cases).2.Comparing the difference of Pin1 expression and absolute counts of Th17 and Treg between RA patients before and after treatment and healthy control group,Kruskal-Wallis rank sum test was used for analysis.The relationship between Pin1 expression and gene RAl data,activity indexes(such as ESR,CRP and DAS28 scores),Th17,Treg and some cytokines in patients with ra was analyzed by Pearson and Spearman correlation test.3.To analyze the expression of Pin1 activity in peripheral blood and the difference of Th17 and Treg expression between the two groups after being treated with low-dose retinoic acid(10 mg twice a week)and traditional immunosuppressants such as hydroxychloroquine for 3 months.Mann-Whitney U test was used for comparison between the two groups,and the difference was statistically significant with P<0.05.Results:1.Compared with the healthy control group [8.97(7.62～11.45)],the activity of Pin1 in peripheral blood of the newly treated RA group was significantly higher[13.62(9.16～19.42)],and the difference was statistically significant(P<0.05).Th17 [18.28(12.76-24.08)] in peripheral blood of the newly treated group of RA was higher than that of the healthy control group [6.04(4.96-7.73)],while Treg [11.06(5.31-21.87)] was significantly lower than that of the healthy control group [40.41(24.33-48.53)].2.The activity of Pin1 in peripheral blood was positively correlated with C-reactive protein,the number of involved joints,DAS-28 score,IL-6,TNF-α(r=0.396,r=0.683,r=0.466,r=0.315,r=0.416),with statistical significance(P<0.05)3.Compared with RA initial treatment group,the expression level of Pin1 activity in RA treatment group [6.94(5.96～8.77)] decreased overall(P<0.05).Compared with the traditional treatment group,the activity of Pin1 in retinoic acid treatment group decreased obviously,but there was no statistical significance.4.Compared with the initial treatment group of RA,Th17[7.38(3.85～11.21)]decreased,while Treg [40.41(17.77～33.47)] increased significantly,and the difference was statistically significant(P<0.05).Compared with the traditional treatment group,Treg[28.9(21.73～37.36)] in retinoic acid treatment group increased significantly,and the difference was statistically significant(P<0.05),but there was no significant difference in Th17 level(P=0.368).Conclusion:1.the activity of Pin1 in the periphe RAl blood of ra patients is over-expressed,which is positively correlated with c-reactive protein,DAS28 score,IL-6 and TNF-α.Pin1 is involved in the pathogenesis of ra patients and reflects the disease activity to a certain extent.2.Th17 in peripheral blood of RA patients increased while Treg decreased significantly,and the activity of Pin1 was negatively correlated with Treg cells.The decrease of Treg cells was related to the high activity of Pin1,which may be one of the main causes of immune imbalance in RA.3.ATRA combined with other traditional drugs can reduce the activity of Pin1 and promote the growth of Treg,which can improve the disease activity of RA patients more effectively to a certain extent. |
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