title: Interleukin-21 is associated with disease activity in patients with Graves' disease.
abstract: 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.
authors.affiliation: Department of Endocrinology and Metabolism, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, 107#, YanJiang West Road, YueXiu District, Guangzhou, 510120, People's Republic of China, zhangjinchina@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Zeng
authors.forename: Meng
authors.initials: M
authors.lastname: Ren
authors.forename: Haiyan
authors.initials: H
authors.lastname: Yan
authors.forename: Mingtong
authors.initials: M
authors.lastname: Xu
authors.forename: Zhimei
authors.initials: Z
authors.lastname: Feng
authors.forename: Weiwen
authors.initials: W
authors.lastname: Liang
authors.forename: Chuan
authors.initials: C
authors.lastname: Yang
authors.forename: Hua
authors.initials: H
authors.lastname: Cheng
authors.forename: Helin
authors.initials: H
authors.lastname: Ding
authors.forename: Li
authors.initials: L
authors.lastname: Yan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006111:Graves Disease / Q000097:blood*; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating / Q000097:blood; D007378:Interleukins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: D018828:Immunoglobulins, Thyroid-Stimulating; D007378:Interleukins; D014284:Triiodothyronine; D013972:Thyrotropin; D000098546:Interleukin-21; D013974:Thyroxine