The associations of circulating CD4⁺CD25^high regulatory T cells and TGF-β with disease activity and clinical course in patients with adult-onset Still's disease

Abstract

Objective. To determine circulating levels of CD4⁺CD25^high regulatory T (Treg) cells and transforming growth factor-β (TGF-β) in patients with adult-onset Still's disease (AOSD) and to examine the associations with disease activity and clinical course of this disease. Methods. The frequencies of circulating CD4⁺CD25^high Treg cells in 52 active AOSD patients, 42 active systemic lupus erythematosus (SLE) patients, and 22 healthy controls (HCs) were determined using flow cytometry analysis. Levels of serum TGF-β and soluble interleukin-2 receptor (sIL-2R) were measured by enzyme-linked immunosorbent assay. Results. Significantly lower levels of circulating CD4⁺CD25^high Treg cells and serum TGF-β were found in AOSD patients and SLE patients than those found in HCs. Levels of circulating CD4⁺CD25^high Treg cells and TGF-β were inversely correlated with disease activity scores for AOSD patients and SLE patients. Circulating CD4⁺CD25^high Treg cell frequencies were positively correlated with serum TGF-β levels for patients with both diseases. Levels of circulating CD4⁺CD25^high Treg cells and TGF-β significantly increased, paralleling clinical remission and the decrease in levels of C-reactive protein and soluble interleukin-2 receptor after effective therapy in AOSD patients. AOSD patients with monocyclic course had significantly higher levels of circulating CD4⁺CD25^high Treg cells and TGF-β compared to those with polycyclic and chronic articular course. Conclusion. Diminished levels of circulating CD4⁺CD25^high Treg cells and TGF-β, and inverse correlation with disease activity in patients with AOSD and SLE might be involved in the pathogenesis of both diseases. Increased levels of circulating CD4⁺CD25^high Treg cells or TGF-β might be associated with a favorable clinical course in AOSD patients.

KEYWORDS:

• CD4⁺CD25^high regulatory T cells
• transforming growth factor-β
• adult-onset Still's disease
• systemic lupus erythematosus
• disease activity