{"title":"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","authors":"Zulvikar Syambani Ulhaq , Zulkarnain Zulkarnain , Lola Ayu Istifiani , Syafrizal Aji Pamungkas , Susiati , Djoko Wahono Soeatmadji , Aulanni’am Aulanni’am","doi":"10.1016/j.endinu.2025.501598","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>IL-6 trans-signaling and imbalance of inflammatory response could be prominent factors in the pathogenesis of GD.</div></div>","PeriodicalId":37725,"journal":{"name":"Endocrinologia, Diabetes y Nutricion","volume":"72 7","pages":"Article 501598"},"PeriodicalIF":0.0000,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Trans-signaling through the agonistic sIL-6R and an imbalanced inflammatory response are associated with increased susceptibility to Graves’ disease\",\"authors\":\"Zulvikar Syambani Ulhaq , Zulkarnain Zulkarnain , Lola Ayu Istifiani , Syafrizal Aji Pamungkas , Susiati , Djoko Wahono Soeatmadji , Aulanni’am Aulanni’am\",\"doi\":\"10.1016/j.endinu.2025.501598\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>IL-6 trans-signaling and imbalance of inflammatory response could be prominent factors in the pathogenesis of GD.</div></div>\",\"PeriodicalId\":37725,\"journal\":{\"name\":\"Endocrinologia, Diabetes y Nutricion\",\"volume\":\"72 7\",\"pages\":\"Article 501598\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-04-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Endocrinologia, Diabetes y Nutricion\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2530016425000643\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"Nursing\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrinologia, Diabetes y Nutricion","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2530016425000643","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Nursing","Score":null,"Total":0}
Trans-signaling through the agonistic sIL-6R and an imbalanced inflammatory response are associated with increased susceptibility to Graves’ disease
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.
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.