Interleukin-21 is associated with disease activity in patients with Graves' disease

Graves' disease (GD) is a common autoimmune disease mainly caused by thyroid-stimulating antibodies (TSAbs). Interleukin 21 (IL-21) has recently been reported to play a vital role in the production of pathogenic autoantibodies in several autoimmune diseases, but less is known about GD. This study aimed to investigate the serum levels of IL-21 in GD patients and to explore their association with disease activity. We performed a case-control association study of 152 patients with GD and 32 healthy controls. All patients were further classified into three subgroups: the GD-untreated group (n = 70), the GD-recurrence group (n = 41), and the GD-remission group (n = 41). Serum IL-21 levels were assayed with ELISA. TSAb activity was measured by an in vitro bioassay. Changes in serum IL-21 were also observed in 12 GD patients before and after treatment. Additionally, correlations among the serum IL-21 and free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroperoxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), thyrotropin receptor antibody (TRAb), and TSAb were also analyzed. The serum IL-21 levels in all GD patients were significantly higher than those in the control group (P < 0.001), and specifically, both the GD-untreated and GD-recurrence groups had elevated serum IL-21 compared to the control group (P < 0.001). Moreover, serum IL-21 in newly diagnosed patients markedly decreased after treatment (P < 0.001). Additionally, the serum IL-21 levels in GD-goiter patients were higher than those of the GD-non-goiter patients (P < 0.001). However, no significant differences were found in the serum IL-21 levels in patients with or without Graves' ophthalmopathy. Importantly, serum IL-21 positively correlated with FT3, FT4, TPOAb, TGAb, and TRAb (r = 0.5053, r = 0.3266, r = 0.1792, r = 0.2445, and r = 0.4096, respectively; all P < 0.0001), and particularly with TSAb activity (r = 0.8171, P < 0.0001), negatively correlated with TSH (r = -0.2713, P < 0.0001). Serum IL-21 levels were significantly elevated in patients with GD and decreased after treatment; moreover, IL-21 may be associated with the clinical disease activity. These observations suggest that IL-21 may play an important role in the pathogenesis of GD.