RESUMO
Objective To observe the changes of number and proportion of CD4+CD25+FOXP3+ cells in peripheral blood of active rheumatoid arthritis patients (RA),and explore the function of recombinant human TNFR Ⅱ-Fc on the CD4+CD25-FOXP3+ Treg cells.Methods ① Forty severe RA patients were selected,who were divided into the combined treatment group (TNFR Ⅱ-Fc+MTX) and MTX only group according to the principle of randomized,double-blind,parallel and placebo-controlled study.All patients were treated for 12 weeks.Flow cytometry was used to analyze and compare the expression ratio of CD4+CD25+FOXP3 +Treg cells of RA patients' peripheral blood.Forty healthy controls were selected for parallel comparison.② VAS,DAS28,HAQ average of the two groups at different periods were compared.Matched t test was used to examine the quantity data between the groups.Results ① The proportion of CD4+CD25+FOXP3+ cells in the peripheral blood of active rheumatoid arthritis patients was significantly lower than healthy group [ (5.4±1.4)％ vs ( 7.5±1.5 )％,P＜0.01 ].The proportion of CD4+CD25+ FOXP3+ Treg cells in combined treatment group was significantly higher [(7.0+1.2)％ vs (5.2±1.6)％,P＜0.01 ] after TNFR Ⅱ-Fc and MTX combination therapy for 12 weeks.The increase rate of CD4+CD25+FOXP3+Treg cells in combined treatment group was evidently more remarkable than MTX only group [ (7.0 ± 1.2)％ vs (5.6 ±0.7 )％,P＜0.01].② After 12 weeks treatment,the arerage scores of VAS,DAS28 and HAQ of the combined treatment group were better than MTX only group,and the difference was statistically significant (P＜0.01).Conclusion This study has shown that the healing effect of TNFR Ⅱ -Fc combined with MTX is better than MTX only.TNFR Ⅱ -Fc can restore and improve the proportion of CD4+CD25+FOXP3+ Treg cells in active RA patients,which is likely to be an important mechanism for the treatment of RA patients.
RESUMO
<p><b>OBJECTIVE</b>To investigate the changes in the circulating levels of Treg cells in patients with rheumatoid arthritis (RA) and their associations with the disease activity.</p><p><b>METHODS</b>The fraction of circulating CD4+CD25+FOXP3+ Treg cells in 40 active RA patients and 40 healthy controls were determined by flow cytometry. The serum levels of interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) were measured using enzyme-linked immunosorbent assay, and the expression of Foxp3 mRNA was detected with real-time PCR. The correlation of the changes in the fraction of Treg cells and the disease activity of RA was analyzed.</p><p><b>RESULTS</b>RA patients showed a significantly lower level of circulating Treg cells than the control subjects [(5.36∓1.55)% vs (7.49∓1.46)%, P<0.01]. The expression of Foxp3 mRNA (P<0.01) and serum IL-10 level (P=0.000) were significantly lower, whereas TGF-β1 significantly higher (P=0.000) in RA patients than in the controls. Spearman analysis showed that serum level of IL-10 but not TGF-β1 was correlated to the fraction of Treg cells and Foxp3 mRNA expression, but the fraction of Treg cells was not correlated to such indices of disease activity as tender joint counts, swollen joint counts, visual analog scale, HAQ, disease activity score in 28 joints, ESR, or CRP, nor to RA self-antibodies (including RF and anti-CCP antibodies).</p><p><b>CONCLUSION</b>A lower fraction and dysfunction of circulating Treg cells might be involved in the pathologies of RA, and a higher disease activity is associated with a greater reduction of Treg cells.</p>
