Trans-signaling through the agonistic sIL-6R and an imbalanced inflammatory response are associated with increased susceptibility to Graves’ disease

4区医学 Q3 Nursing

Endocrinologia, Diabetes y Nutricion Pub Date : 2025-04-30 DOI:10.1016/j.endinu.2025.501598

Zulvikar Syambani Ulhaq , Zulkarnain Zulkarnain , Lola Ayu Istifiani , Syafrizal Aji Pamungkas , Susiati , Djoko Wahono Soeatmadji , Aulanni’am Aulanni’am

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Abstract

Background

Excessive inflammatory cytokines are known to impact immune response and autoimmunity. In this study, we quantified the level of interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), glycoprotein 130 (sgp130) and IL-10 to determine their involvement in the pathogenesis of Graves’ disease (GD), in addition to the assessment serum cytokines IL-6, sIL-6R, sgp130, and IL-10 performance as biomarkers for the diagnosis of GD.

Methods

A total of 20 patients with GD and 21 healthy individuals from the Indonesian population were enrolled. The serum concentrations of the selected cytokines were quantified using the ELISA method. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), and TSH receptor antibody (TSHR-Ab) were also evaluated. Comparative analysis was performed in addition to the assessment of the diagnostic performance of cytokines using receiver-operating-curve (ROC) analysis. Pearson's correlation coefficient was used to assess the relationship between 2 quantitative variables.

Results

Patients with GD had a higher IL-6, sIL-6R, and IL-6/IL-10 ratio but a lower sgp130/sIL-6R/IL-6 ratio vs controls. The ROC curve analysis showed that the sgp130/sIL-6R/IL-6 ratio exhibited better performance than IL-6, sIL-6R, and IL-6/IL-10 ratio in diagnosing GD. In addition, serum levels of IL-6, sIL-6, and IL-10 were associated with thyroid parameters, including TSHR-antibody (Ab) levels.

Conclusion

IL-6 trans-signaling and imbalance of inflammatory response could be prominent factors in the pathogenesis of GD.

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通过激动性sIL-6R的反式信号传导和不平衡的炎症反应与格雷夫斯病易感性增加有关

背景炎性细胞因子过多会影响免疫反应和自身免疫。在本研究中，我们量化了白细胞介素(IL)-6、可溶性IL-6受体（sIL-6R）、糖蛋白130 （sgp130）和IL-10的水平，以确定它们在Graves病（GD）发病中的作用，并评估了血清细胞因子IL-6、sIL-6R、sgp130和IL-10的表现，作为GD诊断的生物标志物。方法从印度尼西亚人群中选取20例GD患者和21例健康人作为研究对象。采用ELISA法定量所选细胞因子的血清浓度。同时检测促甲状腺激素（TSH）、游离甲状腺素（FT4）、游离三碘甲状腺原氨酸（FT3）和TSH受体抗体（TSHR-Ab）。采用受体-工作曲线（ROC）分析对细胞因子的诊断效能进行评价，并进行比较分析。采用Pearson相关系数评价两个定量变量之间的关系。结果GD患者IL-6、sIL-6R和IL-6/IL-10比值高于对照组，但sgp130/sIL-6R/IL-6比值低于对照组。ROC曲线分析显示，sgp130/sIL-6R/IL-6比值在诊断GD方面优于IL-6、sIL-6R和IL-6/IL-10比值。此外，血清IL-6、sIL-6和IL-10水平与甲状腺参数相关，包括tshr抗体（Ab）水平。结论il -6反式信号和炎症反应失衡可能是GD发病的重要因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Endocrinologia, Diabetes y Nutricion Nursing-Nutrition and Dietetics

CiteScore

2.10

自引率

0.00%

发文量

169

审稿时长

35 days

期刊介绍： Endocrinología, Diabetes y Nutrición is the official journal of the Spanish Society of Endocrinology and Nutrition (Sociedad Española de Endocrinología y Nutrición, SEEN) and the Spanish Society of Diabetes (Sociedad Española de Diabetes, SED), and was founded in 1954. The aim of the journal is to improve knowledge and be a useful tool in practice for clinical and laboratory specialists, trainee physicians, researchers, and nurses interested in endocrinology, diabetes, nutrition and related disciplines. It is an international journal published in Spanish (print and online) and English (online), covering different fields of endocrinology and metabolism, including diabetes, obesity, and nutrition disorders, as well as the most relevant research produced mainly in Spanish language territories. The quality of the contents is ensured by a prestigious national and international board, and by a selected panel of specialists involved in a rigorous peer review. The result is that only manuscripts containing high quality research and with utmost interest for clinicians and professionals related in the field are published. The Journal publishes Original clinical and research articles, Reviews, Special articles, Clinical Guidelines, Position Statements from both societies and Letters to the editor. Endocrinología, Diabetes y Nutrición can be found at Science Citation Index Expanded, Medline/PubMed and SCOPUS.