CD4+ CD25+ T regulatory cells and proinflammatory cytokines in Egyptians with rheumatoid arthritis

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Abstract

Objectives

The aim of this study was to measure the levels of CD4+ CD25+ regulatory T (Treg) cells, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-7 in both peripheral blood (PB) and synovial fluids (SFs) from rheumatoid arthritis (RA) patients and to assess their correlation with clinical, laboratory, and activity parameters in an attempt to assess their potential role in the pathophysiology of RA.

Methods

The study included 68 RA patients divided into two groups: group I included 42 patients with active RA and group II included 26 patients with inactive RA. Disease activity was assessed on the basis of disease activity score 28 (DAS 28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti cyclic citrullinated peptide antibodies-3 (Anti-CCP3), and total leukocytic counts. In addition, tumor necrosis factor (TNF-α), interleukin(IL), IL-6 and IL-7 were evaluated. The presence of CD4+ and CD25+ Treg cells was determined by flow cytometry.

Results

The percentage of CD4+ CD25+ Treg cell in the PB peripheral blood was significantly decreased in patients with active RA compared with those with inactive RA and controls. Whereas their percentage was significantly higher in inactive RA compared with active RA and controls. Levels (%) of CD4+ and CD25+ Treg cell, IL-6, TNF-α, and IL-7 in the SF were significantly higher in patients with active RA compared with controls. There was a significant decrease in the percentage expression of CD4+and CD25+ Treg cells in PB compared with SF in group I. The percentage of CD4+ CD25+ Treg cell in PB was inversely correlated with number of swollen and tender joints, disease activity score 28, erythrocyte sedimentation rate, and levels of C-reactive protein, RF, anti-CCP3, TNF-α, IL-6, and IL-7, whereas no significant correlations were found with age and disease duration in both the active and inactive groups.

Conclusion

Active RA patients exhibit a significant reduction in the levels of CD4+ CD25+ Treg cells in PB, which can be considered as a defective immune response that may contribute to the pathogenesis of RA. Hereby, the concept of an increase in the function and/or numbers of Treg cells in the PB and/or joints of RA patients could be an attractive therapeutic goal or novel paradigm in RA treatment.

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