High Interleukin 21 Levels in Patients with Systemic Lupus Erythematosus: Association with Clinical Variables and rs2221903 Polymorphism

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and diverse tissue and organ inflammatory affections. Interleukin 21 (IL-21) is implicated in B cell survival, proliferation, differentiation, class switching, and immunoglobulin production; therefore, it is considered a key cytokine in the pathogenesis of SLE. However, its association with disease activity and clinical phenotypes remains unclear. We aimed to evaluate the association of IL-21 levels with the disease activity and clinical phenotypes in patients with SLE. Also, we analyzed the IL21 polymorphisms associated with increased IL-21 levels. Methods: The IL-21 serum levels were determined using the enzyme-linked immunosorbent assay (ELISA) method. The rs2221903 and rs2055979 polymorphisms were assessed in 300 healthy controls (HCs) and 300 patients with SLE by the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) technique. The levels of IL-21 were monitored during follow-up visits in 59 patients with SLE. Results: The patients with SLE showed higher IL-21 levels compared to the HCs. The IL-21 levels did not correlate with Mex-SLEDAI and were not different in patients with inactive, mild–moderate, and severe disease. The IL-21 levels were increased in patients with hematological affection. The ROC curve analysis revealed that the IL-21 levels had good predictive power in discriminating among patients with SLE and HCs. In a follow-up analysis, the levels of IL-21 remained higher in the patients with SLE even when the patients were in remission. Also, the rs2221903 polymorphism was associated with increased IL-21 levels. Conclusions: This study highlights the importance of IL-21 as a key cytokine in SLE. IL-21 levels are higher in patients with SLE and remain increased regardless of disease activity. According to the ROC analysis, IL-21 is a potential biomarker of SLE. Further longitudinal studies are needed to explore the relationship between IL-21 and the clinical phenotypes of SLE.