Reduction of forkhead box P3 levels in CD4+CD25high T cells in patients with new-onset systemic lupus erythematosus

Abstract

Summary The aim of this study was to quantify and evaluate the forkhead box P3 (FoxP3) expression regulatory T cells in new-onset systemic lupus erythematosus (SLE) patients before and after treatment. Forty-four newly diagnosed and untreated SLE patients, including 24 with active disease (SLEDAI ≥ 10) and 20 with inactive disease (SLEDAI < 5), were enrolled in this study. Twenty-one age- and sex-matched healthy volunteers were also included as controls. Peripheral blood samples were collected and mononuclear cells isolated. The expression of CD25 and FoxP3 in CD4+ T cells were analysed with flow cytometry. CD4+CD25+ (3·95–13·04%) and CD4+CD25high (0·04–1·34%) T cells in peripheral blood in untreated patients with new-onset active lupus were significantly lower than that in the patients with inactive lupus (7·27–24·48%, P < 0·05 and 0·14–3·07% P < 0·01 respectively) and that in healthy controls (5·84–14·84%, P < 0·05). Interestingly, the decrease in CD4+CD25high T cells was restored significantly in patients with active lupus after corticosteroid treatment. There was, however, a significantly higher percentage of CD4+FoxP3+ T cells in patients with active (5·30–23·00%) and inactive (7·46–17·38%) new-onset lupus patients compared with healthy control subjects (2·51–12·94%) (P < 0·01). Intriguingly, CD25 expression in CD4+FoxP3+ T cells in patients with active lupus (25·24–62·47%) was significantly lower than that in those patients with inactive lupus (30·35–75·25%, P < 0·05) and healthy controls (54·83–86·38%, P < 0·01). Most strikingly, the levels of FoxP3 expression determined by mean fluorescence intensity in CD4+CD25high cells in patients with active SLE were significantly down-regulated compared with healthy subjects (130 ± 22 versus 162 ± 21, P = 0·012). CD4+CD25high T cells are low in new-onset patients with active SLE and restored after treatment. Despite that the percentage of CD4+FoxP3+ T cells appear high, the levels of FoxP3 expression in CD4+CD25high T cells are down-regulated in untreated lupus patients. There is a disproportional expression between CD25high and FoxP3+ in new-onset patients with active SLE.