Peripheral Blood Of Patients With Rheumatoid Arthritis Th17 Cells In Expression Level And Its Clinical Relevance

Background.Th17 is a newly defined subgroup of CD4(+)effecor T cells,and is considered to be one of the key T cell lineages in the development of a large scale of autoimmune diseases,including rheumatoid arthritis.Th17 is characteristic by its secretion of specific spectrum of cytokines,including IL-17,which is a important upstream cytokine in the chronic inflammation and bone destruction of RA.It has been demonstrated that both Th17 and its cytokines are up regulated in RA synovial tissue, and treatment commits their down regulation.However,these researches are mostly focused on Th17 expression in synovial fluid and tissue,and there is still limited understanding of its peripheral expression,and its correlation with clinical symptoms and effects of treatment.Objective.To assess the peripheral expression of Th17 cells in RA patients and its clinical correlations.Investigate into the effects of DMARDs or anti-TNF-αtherapy on Th17 expression,and the correlation of its expression with clinical disease remission. Methods.20 RA patients with active disease were separately treated with DMARDs(n=10) and adalimumab(n=10).Blood samples were taken for laboratory analysis at week 0 and week 12 of treatment for DMARDs treated group,and week0, week12 and week24 of adalimumab treated group.Laboratory methods used include the following:flowcytometry for detection of PBMC CD4(+)IL-17(+) cells and their MFI; RT-PCR for semi-quantitatively determination of mRNA expression of IL-17,RORc and FOXP3;ELISA detection of serum IL-17 and IL-6.Same tests were run on age and sex marched normal controls(n=10).Results.Flowcytometry.PBMC CD4(+)IL-17(+)T cell was significantly up regulated in RA patients,and positively correlated with disease activity.PBMC Th17 cell count decreased significantly by week 12 of treatment.The baseline Th17 level of DMARDs treated group and the mean Th17 level during Adalimumab treatment were significantly negatively correlated with clinical remission(p＜0.05).RT-PCR.PBMC FOXP3 mRNA expression was significantly down regulated in RA patients,and negatively correlated with disease activity,and IL-17 gene expression was significantly positively correlated with ESR. FOXP3 mRNA expression was significantly up regulated by week 12 of treatment(p＜0.05). ELISA.Serum IL-6 level was significantly up regulated in RA patients,and decreased significantly with treatment(p＜0.O5). Conclusion.The PBMC Th17 cell count and IL-6 serum level were significantly up regulated in RA patients,and there was significant down regulation of FOXP3 mRNA expression.PBMC Th17 count and IL-17 mRNA expression positively correlated with disease activity,and FOXP3 gene expression had a negatively correlation.DMARDs and Adalimumab treatment decreased PBMC Th17 cell count and serum IL-6 level significantly,and increased FOXP3 expression,indicating that treatment might be effected through Th17 and Treg modulation.For DMARDs treated patients,baseline Th17 cell count was a predictive factor of disease remission with treatment,and for the Adalimumab treated group,this predictive effect is weakened,which might be attributed to that blockade of TNF-αalso blocked its positive feedback effects on Th17 cells.However,mean Th17 expression during adalimumab treatment was negatively correlated with disease remission,indicating that high level of Th17 cells might impact on the effectiveness of anti-TNF-αtherapy,and molecular targeting towards Th17 might be the new direction of RA treatment.