Increased Human Interleukin-32 Expression Is Related to Disease Activity of Graves' Disease.

Qiuming Yao,Wei Yao,Bin Wang,Jin-An Zhang,Qian Li,Xi Jia

doi:10.3389/fendo.2019.00613

Abstract

Recently, abnormal expression of interleukin-32 (IL-32) has been involved in various inflammatory or autoimmune diseases, but the level of IL-32 expression in Graves' disease (GD) is still unknown. This study is aimed to explore the human IL-32 expression in GD and the association of IL-32 expression with the disease activity of GD. A total of 125 GD patients and 97 normal controls (NC) were recruited in this study. We examined IL-32 mRNA level in peripheral blood mononuclear cells (PBMCs) of 43 GD patients and 41 controls using real-time polymerase chain reaction (RT-PCR). Serum IL-32 level of 40 GD patients and 34 controls was measured by enzyme linked immunosorbent assay (ELISA). In another cohort including 42 GD patients and 22 controls, we detected the percentages of IL-32α+ cells, CD4+IL-32α+T cells, and CD4−IL-32α+ cells in PBMCs by flow cytometry. In GD patients, IL-32 mRNA expression was dramatically higher than that in controls (P < 0.001) and positively associated with FT3 (P = 0.036, r = 0.321). Subgroup analysis revealed that IL-32 mRNA level was elevated in both newly onset GD and refractory GD group (P < 0.01, P < 0.001, respectively) compared with controls. Furthermore, in refractory GD group, the IL-32 mRNA expression also positively correlated with FT3 (P = 0.019, r = 0.560). In addition, serum IL-32 level was notably higher in GD patients than that of controls (P < 0.01). Subgroup analysis also indicated that serum IL-32 level in both newly onset GD and refractory GD group was higher in comparison with controls (P = 0.015, P = 0.023, respectively) and serum IL-32 level in refractory GD patients positively correlated with TRAb (P = 0.043, r = 0.481). The percentages of IL-32α+ cells, CD4+IL-32α+ T cells, and CD4−IL-32α+ cells were all significantly enhanced in GD patients compared with controls (P = 0.005, P = 0.017, P = 0.016, respectively). IL-32 and IL-32α+ cells may be associated with the pathogenesis of GD. IL-32 may become a promising target for the treatment of GD.

Highlights

Graves’ disease (GD) is a common organ-specific autoimmune disease characterized by hyperthyroidism and positive serum thyrotrophin receptor antibody (TRAb)
We firstly revealed that IL-32 mRNA and IL32α+ cells in peripheral blood mononuclear cells (PBMCs) of GD patients were dramatically increased compared with that of healthy controls
In myasthenia gravis (MG) patients, serum IL-32α level was significantly higher compared with healthy controls and tended to reduce with clinical improvement [27]

Summary

Introduction

Graves’ disease (GD) is a common organ-specific autoimmune disease characterized by hyperthyroidism and positive serum thyrotrophin receptor antibody (TRAb). Symptoms of some patients are accompanied by ophthalmopathy and dermopathy. GD can be associated with other systemic autoimmune diseases. It has been reported that the most common autoimmune disease associated with GD patients is vitiligo, followed by chronic autoimmune gastritis and rheumatoid arthritis [4]. Many studies have shown that a variety of cytokines are related to GD’s pathogenesis and can influence its severity or prognosis [5,6,7,8,9], and peroxisome proliferator activated receptor (PPAR)-γ and α agonists can modulate CXCR3 chemokines that are implicated in the pathogenesis of Graves’ disease [10, 11].

Objectives

Methods

Results

Conclusion