| Background Rheumatoid arthritis(RA)is a kind of autoimmune disease characterized by joint damage.recently,most of the research mainly focuses on the joint,RA also cause systemic involvement such as cardiovascular,kidney,blood,nerves and other system damage[1].RA pathogenesis is a more complex course,and it has been confirmed that many of the cytokines involved in it.some biological dmards have been successfully used in clinical practice,but some patients still continue to be serious,So we need to study the pathogenesis of RA may involve the regulation of cytokines and signaling pathway.IL-6 is a multi-functional cytokines,which plays an important role in the pathogenesis of RA,and it participates in the formation of pannus,causing bone and cartilage damage [2].And it may cause heart,lung,kidney and other system damage.In recent years,it has been found that Th17 cell is an important style of T cells.The interleukin-17(IL-17)secreted by Th17 cells plays an important role in immune regulation[3].IL-17 plays an important role in the pathogenesis of RA.Janus Kinase/Signal transducers and activators of transcription(JAK / STAT)signaling pathways are the hotspots of RA research in recent years.IL-6,TNF-α,IL-17,IL-21 and other cytokines play roles in the pathogenesis of RA by affecting the JAK-STAT pathway which is active.Inhibition of JAK pathway can improve the pathology of RA.IL-6 promotes the expression of matrix metalloproteinases(MMPs),such as MMP-1,MMP-3 and MMP-13 in the synovial fibroblasts by influencing STAT pathway,causing joint and cartilage damage.Tocllizumab injection is a recombinant humanized monoclonal antibody that not only improves the joint symptoms of RA patients,relieves the disease activity,but also improves the performance of RA system damage,including correcting anemia,improving depression and so on.Tocllizumab injection also be used in other diseases,such as adult onset of Still’s disease,giant cell arteritis and so on.Compared with other biological dmards,it is safer and stable,but we still need to pay close attention to its adverse reactions,including infection,liver damage,rash and so on.There are rare studies about relationship of IL-6,IL-17,JAK3,STAT3,MMP-3 and MMP-13 in RA system damage and disease activity.This study intends to explore their relationship with RA system damage and disease activity.Objections 1.To explore the relationship between IL-6,IL-17,JAK3,STAT3,MMP-3,MMP-13 and the activity of RA disease by measuring the serum levels of them.2.To investigate the system damage of RA,and analyze its influencing factors;To explore the relationship between IL-6,IL-17,JAK3,STAT3,MMP-3,MMP-13 and RA system damage.Methods 1.Serum levels of IL-6 and IL-17 were measured by enzyme-linked immunosorbent assay(ELISA)in 124 patients with RA and 48 normal controls.To investigate the relationship between IL-6,IL-17 and system damage and disease activity2.136 RA patients and 40 healthy people were selected,recorded the clinical,laboratory,ultrasound and imaging data,system damage and treatment.The levels of IL-6,JAK3,STAT3,MMP-3 and MMP-13 in serum were detected by ELISA and analyzed their relationship.Results 1.correlation between IL-6,IL-17 and RA disease activity,system damage1.1 The levels of serum IL-6 and IL-17 in RA group were significantly higher than those in normal group,The levels of serum IL-6 and IL-17 in the patients with moderate to severe disease were significantly higher than those in the low disease activity group,The levels of serum IL-6 in the low disease activity group were significantly higher than those in the normal group.The difference was statistically significant(P <0.05).1.2The incidence rate of system impariment in RA was 68.55%,which including cardiovascular 34 cases(27.42%),respiratory system 18 cases(14.52%),hematologic system 53 cases(42.74%),urinary system 14 cases(11.29%),digestive system12 cases(9.68%),endocrine system 10 cases(8.06%),nerve and skeletal system 8 cases(6.45%).The incidence rate of system impariment in the patients with low disease activity was 52.27%,and the rate in the patients with moderate to severe activity was 77.5%.There were significant differences in cardiovascular,respiratory and blood system between the two groups(P <0.05).1.3The DAS28 and CRP levels showed higher level in patients with system impairment than without system impairment(P<0.01).1.4There was a significant positive correlation between IL-6 and SJC,TJC,VAS score,Pt GA score,PGA score,CRP,ESR,platelet count,globulin level and DAS28(P <0.05);IL-17 and TJC,VAS score,Pt GA score(P <0.05),PGA score,RF,CRP,ESR,uric acid and DAS28 were positively correlated(P <0.05).1.5 There were 60 patients(63.83%)with systemic damage in the treatment group and 25 cases(83.33%)in the non-normal treatment group,the difference was statistically significant(P <0.05).The levels of DAS28 and CRP were significantly decreased in the normal treatment group.2.correlation between IL-6,JAK3,STAT3,MMP-3,MMP-13 and RA disease activity,system damage2.1The levels of serum IL-6,JAK3,STAT3 and MMP-13 in RA patients were significantly higher than those in normal group(P <0.05).IL-6 and JAK3 were significantly higher in the moderate to severe activity group(DAS≥3.2)than those in the low-disease group(DAS28 <3.2)(P <0.05).2.2The rate of system involvement in RA was 69.85%,including cardiovascular 44 cases(32.35%),respiratory system 40 cases(29.41%),hematologic system 38 cases(27.94%),urinary system 14 cases(10.29%),digestive system 22 cases(16.18%),endocrine system 10 cases(7.35%),skeletal system 8 cases(5.88%).nerve system 9cases(6.62%);Serum level of JAK3 and STAT3 were markedly higher in group of system involvement(P<0.05).2.3Positive correlation was revealed between serum IL-6 and ESR,CRP and HAQ by single linear regression analysis,and negatively correlated with course of the disease;Positive correlation was revealed between serum JAK3 and anti-CCP antibody、STAT3;STAT3 was positively correlated with anti-CCP antibody,JAK3 and system involvement(P<0.05).JAK3 was still positively correlated with STAT3 by multiple linear regression analysis,STAT3 was positively correlated with anti-CCP antibody and JAK3;IL-6 was still negatively correlated with course of the disease.Multiple logistic regression analysis revealed that course of the disease and platelet were risk factors for cardiovascular system damage;CRP was a risk factor for respiratory system;course of the disease was risk for endocrine system;IL-6 was risk for skeletal system(P<0.05).2.4.Compliance treatment and RA system damage2.4.1 The incidence of systemic damage was 62.22% in the normal treatment group and 84.78% in the untreated group(P <0.05).The DAS28 score and STAT3 level in the normal treatment group were significantly lower than those in the untreated group(P <0.05).2.4.2 There were 22 cases(48.89%)with systemic damage in the standard group,and 73 cases(80.22%)had no systematic damage.The difference was statistically significant(P <0.05).Conclusions1.The rate of RA system damage was higher.In both cases,the incidence was significant in the two groups.The incidence of system damage was significantly lower in the low disease group than in the moderate to severe group.Disease relief is good for reducing the incidence of system damage.2.The levels of IL-6,IL-17,JAK3,STAT3 and MMP-13 in the RA group were significantly higher than those in the normal group.The levels of serum IL-6,IL-17 and JAK3 in moderate and severe activity group were significantly higher than those in low disease group,which affected RA disease activity.3.The levels of JAK3 and STAT3 in the system damage group were significantly increased,and the two cytokines might be related to the damage of RA system. |
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