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Inverse correlation between CD4 + regulatory T‐cell population and autoantibody levels in paediatric patients with systemic lupus erythematosus

2006; Wiley; Volume: 117; Issue: 2 Linguagem: Inglês

10.1111/j.1365-2567.2005.02306.x

1365-2567

Jyh‐Hong Lee, Li‐Chieh Wang, Yu‐Tsan Lin, Yao‐Hsu Yang, Dong‐Tsamn Lin, Bor‐Luen Chiang,

Atherosclerosis and Cardiovascular Diseases

Summary CD4 + CD25 + regulatory T cells (Tregs) are critical in maintaining self‐tolerance and preventing organ‐specific autoimmunity. Their role in paediatric systemic lupus erythematosus (SLE), an autoimmune disease characterized by inappropriate regulation of hyperactivated B and T cells, has not been clearly defined. Using flow cytometry to determine cell populations and real‐time polymerase chain reaction to assay mRNA expression for FOXP3, CTLA‐4, and GITR, we characterized CD4 + CD25 + T cells in paediatric SLE patients and healthy subjects. The frequency of CD4 + CD25 + Tregs was significantly decreased in patients with active SLE compared with patients with inactive SLE and with controls (7·27% ± 2·50%, 9·59% ± 2·80% and 9·78% ± 2·11%, respectively; P = 0·027 and P < 0·001, respectively), and was inversely correlated with disease activity, as assessed with the Systemic Lupus Erythematosus Disease Activity Index 2000 scores ( r = −0·59, P = 0·001) and serum anti‐double‐stranded DNA levels ( r = −0·65, P < 0·001). Our preliminary investigations found elevated surface expression of GITR in CD4 + CD25 + T cells, elevated mRNA expression of CTLA‐4 in CD4 + T cells and higher amounts of mRNA expression for FOXP3 in CD4 + cells in patients with active SLE compared with patients with inactive disease and controls. We demonstrated reduced CD4 + CD25 + Treg levels were inversely correlated with disease activity, indicating a defective Treg population in paediatric SLE patients. The differences in the expression of FOXP3, CTLA‐4 and GITR imply the possible role of CD4 + Tregs in the pathogenesis of SLE.