Decreased Interleukin 35 and CD4+EBI3+ T cells in Patients With Active Systemic Lupus Erythematosus

Background: Interleukin 35 (IL-35) is likely to contribute to the development of autoimmune diseases, as the Epstein-Barr virus-induced gene protein 3 (EBI3) is the specificity subunit of IL-35. Nevertheless, until recently, no studies have evaluated its role in systemic lupus erythematosus (SLE) in humans. The objective of this study was to investigate the serum IL-35 level and the percentage of CD4(+)EBI3(+) T cells in the peripheral blood of patients with SLE and explore the roles of double-positive T cells and IL-35 in the pathogenesis of SLE and the effects of glucocorticoid on these roles. Methods: Fifty-five hospitalized patients with SLE were recruited, and 20 volunteers were enrolled as healthy controls. Serum IL-35 levels were measured by enzyme-linked immunosorbent assay, and the percentage of CD4(+)EBI3(+) T cells was analyzed by flow cytometry. Results: The serum IL-35 level and the percentage of CD4(+)EBI3(+) T cells were significantly decreased in patients with active SLE compared with healthy controls and patients with inactive SLE. The serum IL-35 level and the percentage of CD4(+)EBI3(+) T cells were negatively correlated with the SLE disease activity index. The percentages of CD4(+)EBI3(+) T cells and serum IL-35 levels in 10 untreated patients with active SLE were increased at days l, 3, and 7 after the treatment with methylprednisolone (0.8 mg.kg(-1).d(-1)) compared with the percentages before the treatment. Conclusions: These results demonstrate that abnormalities in IL-35 and CD4(+)EBI3(+) T cells may play important roles in the pathogenesis of SLE; the percentage of double-positive T cells and the level of IL-35 are parameters for the evaluation of SLE activity and severity.