Background Interleukin-21 (IL-21) has various effects on a number of immune cells including B cells, T cells, natural killer (NK) and NKT cells. One of the essential roles of IL-21 is to contribute to autoantibody production as a result of promoting hyperactivity of B cells. Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by pathogenic autoantibody production and systemic organ damage. A few studies have been conducted for investigating the contribution of IL-21 to the pathogenesis of murine SLE. However, only limited studies have been performed concerning the role of IL-21 in human SLE and the results are still controversial.
Objectives The aim of this study was to evaluate whether IL-21 participates in the pathogenesis of human SLE.
Methods Serum IL-21 levels were measured in SLE, osteoarthritis (OA) patients and healthy controls (HC). Serum IL-21 levels were analyzed for revealing the correlation with laboratory data or a disease activity index for SLE. Kidney tissues from patients with lupus nephritis and controls were used for evaluating the expression of IL-21 and IL-21R. Normal portions of human kidneys removed for renal carcinoma were used as normal controls.
Results Serum levels of IL-21 were increased in the patients with SLE as compared to the patients with OA or HC. Serum IL-21 levels of the patients with SLE were positively correlated with serum levels of IgG, the titers of anti–double-stranded DNA antibodies and the scores of SLE Disease Activity Index. SLE patients with low C4 concentrations had higher serum IL-21 levels than those with normal C4 concentrations. The expression of IL-21 was higher in renal tubular epithelial cells of the patients with lupus nephritis than in those of controls.
Conclusions This study reveals the association between IL-21 and disease activity in the patients with SLE. We also first demonstrate IL-21 expression in renal tissue of the patients with lupus nephritis. These findings suggest that IL-21 is critically implicated in the pathogenesis of SLE.
Ettinger R, Kuchen S, Lipsky PE: Interleukin 21 as a target of intervention in autoimmune disease. Annals of the rheumatic diseases 2008, 67 Suppl 3:iii83–86.
Herber D, Brown TP, Liang S, Young DA, Collins M, Dunussi-Joannopoulos K: IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression. Journal of immunology 2007, 178(6):3822–3830.
Disclosure of Interest None declared