Association between high mobility group box-1 circulation level and Graves' ophthalmopathy

Abstract

Background: Graves' disease is a prevalent autoimmune disorder that causes hyperthyroidism. Despite being widely recognized, the risk factors for its associated condition, ophthalmopathy, are not well understood. High Mobility Group Box 1 (HMGB1), a damage-associated molecular pattern biomarker, has been linked to autoimmune diseases and may play a role in Graves' ophthalmopathy. The aim of this study is to assess the correlation between the levels of circulating HMGB1 and the occurrence of Graves' ophthalmopathy (GO). Methods: This cross-sectional study evaluated 44 recently diagnosed Graves' disease patients at Sardjito Hospital. The presence of Graves' ophthalmopathy (GO) was determined using criteria set by Bartley and Gormans. The levels of HMGB1 were measured in the blood of both groups (22 GO patients and 22 controls without GO) using ELISA. Statistical analysis, including binomial logistic regression and Mann-Whitney test, was conducted to analyze the data and adjust for confounding factors with multinomial logistic regression. Results: The baseline characteristics of 22 GO patients and 22 non-GO patients were similar, including age (30.91±6.06 vs. 30.68±6.63 years, p>0.05), gender distribution (77.3% vs. 81.8% female, 22.7% vs. 18.2% male, p>0.05), and duration of diagnosis (5.13±2.21 vs. 4.82±1.89 months, p>0.05). However, a significant difference (p<0.001) was found in the levels of circulating HMGB1, with GO patients having a median value of 15.49 pg/mL (5.12-47.59 pg/mL) compared to 2.33 pg/mL (0.82-15.66 pg/mL) in the control group. The risk of developing ophthalmopathy increased 12 times when Graves disease patients had HMGB1 levels above 8.86 pg/mL. Conclusion: The study found a significant association between elevated levels of HMGB1 (> 8.86 pg/mL) and an increased risk (12 times) of Graves’ ophthalmopathy in newly diagnosed Graves' disease patients. The results suggest that HMGB1 may be a potential biomarker for predicting the development of ophthalmopathy in Graves' disease patients.