Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; Traditional Herb Medicine Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei 11031, Taiwan; Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei 11031, Taiwan.
Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11031, Taiwan.
Cytokine. 2021 Feb;138:155353. doi: 10.1016/j.cyto.2020.155353. Epub 2020 Oct 26.
Inflammatory cytokines participate in immune reactions and the pathogenesis of autoimmunity. Herein, we quantified four groups of inflammatory cytokines, including interferons (IFNs), the tumor necrosis factor (TNF) superfamily (TNFSF), interleukin (IL)-related cytokines, and bone and extracellular matrix remodeling-related cytokines to determine their contributions in women with overt Graves' disease (GD).
Forty-three women with GD were enrolled in this cross-sectional study. Thirty-seven cytokines, thyroid-stimulating hormone (TSH), free thyroxine, and TSH receptor antibody (TSHRAb) were quantified. GD patients with a low TSH level at the time of sample collection were defined as having active GD.
Patients with active GD had higher IFN-α2, IFN-γ, IFN-λ1, and IFN-λ2 levels than those with inactive GD. In addition, certain TNFSF cytokines, including soluble cluster of differentiation 30 (sCD30), TNFSF member 14 (TNFSF14), pentraxin (PTX)-3, soluble TNF receptor 2 (sTNF-R2), and thymic stromal lymphopoietin (TSLP) were higher in active GD than in inactive GD. Moreover, active GD patients had higher IL-2, IL-12(p40), osteocalcin (OCN), and matrix metalloproteinase (MMP)-3 than inactive GD patients. All IFNs except IFN-λ1 were correlated with TSHRAb titers. Moreover, TNFSF cytokines, consisting of B-cell-activating factor, sCD30, TNFSF14, PTX-3, sTNF-R2, and TSLP, were associated with TSHRAb levels.
Serum IFNs could be the most remarkable cytokines in modulating the disease severity and TSHRAb titers in women with full-blown GD. Further molecular-based research to clarify the actual role of IFNs in the disease progression of GD is needed.
炎症细胞因子参与免疫反应和自身免疫的发病机制。在此，我们定量了包括干扰素（IFNs）、肿瘤坏死因子（TNF）超家族（TNFSF）、白细胞介素（IL）相关细胞因子和骨与细胞外基质重塑相关细胞因子在内的四组炎症细胞因子，以确定它们在显性 Graves 病（GD）女性中的作用。
本横断面研究纳入了 43 名 GD 女性患者。检测了 37 种细胞因子、促甲状腺激素（TSH）、游离甲状腺素和 TSH 受体抗体（TSHRAb）。采集样本时 TSH 水平低的 GD 患者被定义为活动期 GD。
与非活动期 GD 相比，活动期 GD 患者的 IFN-α2、IFN-γ、IFN-λ1 和 IFN-λ2 水平更高。此外，某些 TNFSF 细胞因子，包括可溶性 CD30（sCD30）、TNFSF 成员 14（TNFSF14）、五聚素 3（PTX-3）、可溶性 TNF 受体 2（sTNF-R2）和胸腺基质淋巴细胞生成素（TSLP）在活动期 GD 中也高于非活动期 GD。此外，活动期 GD 患者的 IL-2、IL-12（p40）、骨钙素（OCN）和基质金属蛋白酶（MMP）-3 水平高于非活动期 GD 患者。IFN-λ1 以外的所有 IFN 均与 TSHRAb 滴度相关。此外，TNFSF 细胞因子（包括 B 细胞激活因子、sCD30、TNFSF14、PTX-3、sTNF-R2 和 TSLP）与 TSHRAb 水平相关。
血清 IFNs 可能是调节女性 GD 患者疾病严重程度和 TSHRAb 滴度的最显著细胞因子。需要进一步的基于分子的研究来阐明 IFNs 在 GD 疾病进展中的实际作用。
