Background Previously we have shown that interleukin-21 (IL-21) level was tightly associated with anti-nuclear antibody (ANA) production in cultured peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE) , suggesting a role for this cytokine in the disease onset. In addition to working on the expansion and maintenance of the Th17 lineage, IL-21 is also an important growth factor for T follicular helper (TFH) cells, thus could accelerate the production of pathogenic autoantibodies.
Objectives To detect the levels of IL-21 and TFH cells as well as Th17 cells in Chinese SLE patients and to find out their relationships with disease activity, plasma cells and autoantibody levels.
Methods Sixty-two adult SLE patients and 23 healthy subjects matched for gender and age were recruited. Disease activity was evaluated by the SLE disease activity index (SLEDAI) score. Proportion of circulating TFH cells (CXCR5+PD1+/CD4+), Th17 cells (CCR6+/CD4+) and plasma cells (CD19+CD138+) were measured by flow cytometry. Serum levels of IL-21, ANA and anti-double strand DNA (dsDNA) antibody were assessed by ELISA. To determine the effect of IL-21 on TFH cells, PBMCs from SLE patients were collected and cultured with or without human recombinant IL-21 (200ng/ul) in a tissue culture incubator and then harvested for TFH measuring at 24 and 72 hours.
Results Proportion of circulating TFH cells and serum IL-21 levels were elevated in SLE patients comparing to those in normal controls, while there was no difference of Th17 cells between the two groups. TFH cells, but not IL-21 levels, were positively correlated with SLEDAI score, CD19+CD138+ plasma cells, serum ANA and anti-dsDNA titers in SLE patients. When recombinant IL-21 was added to PBMC culture systems, there was a significant increase of TFH cell proportions.
Conclusions TFH cells contribute to disease activity and autoantibody production in SLE patients. IL-21 may act through the upregulation of TFH cells to play a role in the pathogenesis of SLE.
Feng X, Li R, Huang J, Zhang H, Zhu L, Hua B, Tsao BP, Sun L. Olf1/EBF associated zinc finger protein interfered with antinuclear antibody production in patients with systemic lupus erythematosus. Arthritis Res Ther. 2010;12(2):R59.
Disclosure of Interest None Declared