The Role Of Th1/Th17and Treg Cells In The Formation And Development Of Joint Inflammation In Patients With Rheumatoid Arthritis

Objective：Rheumatoid arthritis (RA) is an autoimmune disease with the featureof joint inflammation. The helper T lymphocytes is a group of importantcells which mediate inflammation.These cells play a significant role inthe pathogenesis of RA.We intend to study the changes of Th1/Th17andTreg cells in peripheral blood and synovial fluid of patients with activeRA, and its correlation with disease activity and clinical indicators ofinflammation. Further more, we would discuss and provide theoreticaland experimental evidence to reveal the molecular mechanisms of RA.Methods:Twenty patients with active RA and15normal people were includedin this study according to the inclusion and exclusion criteria. Theperipheral blood and synovial fluid of patients with active RA arecollected and divided into different experimental groups. Peripheral bloodof normal people is taken as the control group. The peripheral bloodmononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC)were isolated by density gradient centrifugation. The PBMC and SFMCwere colony-stimulating cultured and stained，then, Th1/Th17and Treg cells in peripheral blood and synovial fluid were detected by flowcytometry. The peripheral blood of20patients with active RA werecollected to detect the fasting blood erythrocyte sedimentation rate (ESR),C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinatedpeptide antibody (ACPA). Joint inflammation and the DAS28score ofpatients with RA were then evaluated and calculated. Statistical analysesof all data were done by using SPSS17.0software.Results:1. The rate of Th1cells in the peripheral blood of normal controlgroup was (5.26±0.55)%, while that in the peripheral blood of patientswith active RA was (7.44±1.46)%, and (19.83±3.18)%in synovialfluid of these people. The proportion of Th1cells was higher in theperipheral blood of patients with active RA than the normal control group（P<0.05）. The proportion of Th1cells was higher in synovial fluid thanin the paired peripheral blood (P <0.01) and the normal control group (P<0.01).2. The rate of Th17cells in the peripheral blood of normal controlgroup was（0.37±0.13）%, while that in the peripheral blood of patientswith active RA was（1.14±0.42）%, and（1.98±0.67）%in synovial fluidof these people. The proportion of Th17cells was higher in the peripheralblood of patients with active RA than the normal control group（P<0.01）.The proportion of Th17cells was higher in synovial fluid than in the paired peripheral blood (P <0.01) and the normal control group (P<0.01).3. The rate of Treg cells in normal human peripheral blood was（3.81±0.56）%, while that in the peripheral blood of patients with activeRA was（2.92±0.66）%, and（5.10±1.76）%in synovial fluid of thesepeople. The proportion of Treg cells was higher in the peripheral blood ofpatients with active RA than the normal control group (P <0.05).Theproportion of Treg cells in synovial fluid was higher than in the pairedperipheral blood (P <0.05) and the normal control group (P <0.01).4. The proportion of Th17cells in peripheral blood was correlatedwith the number of swellon joints、tender joints and DAS28score（r=0.593，P=0.006；r=0.625，P=0.003；r=0.777，P=0.001).5. The proportion of Th17cells in synovial fluid was correlated withCRP（r=0.887，P=0.001).Conclusions:1. Compared with normal control group, the proportion of pro-inflammatory cells such as Th1cells and Th17cells in the peripheralblood and synovial fluid of patients with active RA was increased. Theproportion was even higher in synovial fluid. The proportion of Th17cells in peripheral blood was correlated with the number of swellon joints,tender joints and DAS28score. The proportion of Th17cells in synovialfluid was correlated with CRP. There was no significant correlation between the proportion of Th1cells in peripheral blood and clinicalinflammatory indicators (swollen joints, tender joints, ESR, CRP, RF,ACPA and DAS28score). Our results suggest that the Th17cells andIL-17play the crucial role in the development of joint inflammation ofRA. Th17cells may be one of the indicators of the activity of RA.2. The proportion of Treg cells in the peripheral blood of patientswith active RA was lower than that in the normal control group. But theproportion of Treg cells in the peripheral blood was higher than that in thepaired synovial fluid of patients with active RA. The proportion of Tregcells in both peripheral blood and synovial fluid showed no significantcorrelation with the clinical inflammatory indicators (swollen joint count,tender joint, ESR, CRP, RF, ACPA and DAS28score) of RA. Treg cellscouldn’t reflect the changes of systemic inflammation in patients with RA.Whether there was a link between the infiltration of Treg cells in RAsynovial fluid and the joint inflammation was under further research.