CHIA-HUNG LINLee, Yi-ChiehYi-ChiehLeeHsiue, Yen-ChungYen-ChungHsiueYI-HSUAN WEIYang, Chung-YiChung-YiYangKANG-CHIH FANLee, Chung-WeiChung-WeiLeeI-WENG YENLu, ChingChingLuHuang, Tse-YingTse-YingHuangLin, Chun-HsienChun-HsienLinSHYANG-RONG SHIH2026-03-102026-03-102026-01-01https://scholars.lib.ntu.edu.tw/handle/123456789/736160Background: Graves’ orbitopathy (GO) profoundly affects patients’ quality of life, even in its mild form, yet the underlying factors contributing to this impairment remain underexplored. Recent evidence suggests the potential immune tolerance-inducing effect of immunoglobulin G4 (IgG4) in the pathogenesis of GO. However, its specific impact on quality of life and its significance in mild GO have not been well characterized. Methods: This prospective multicenter study included patients with mild GO who were in euthyroidism. Quality of life was assessed using the validated GO-quality of life questionnaire (GO-QoL). Serum IgG4 levels and IgG4/IgG ratios were measured and analyzed in relation to GO-QoL scores and other clinical and biochemical parameters. Results: Patients with mild GO exhibited significantly impaired quality of life, with the greatest impact seen in the appearance subscale. Notably, serum IgG4 levels were positively correlated with visual functioning scores in the GO-QoL (ρ = 0.248, P = 0.0466). Higher serum IgG4 levels were also associated with less limitation in driving and a longer duration of GO. Moreover, serum IgG4 levels and IgG4/IgG ratios showed significant positive correlations with male sex and clinical activity score. Conclusions: This study highlights the significant impairment in the quality of life experienced by patientswithmild GO and identifies serum IgG4 as a promising indicator for evaluating disease chronicity and quality of life, which may help guide different treatment strategies. Further prospective and basic studies are required to explore the role of IgG4 in the pathogenesis of GO.enGraves’ orbitopathyimmunoglobulin G4quality of lifethyroid eye diseasejournal article10.1530/EC-25-058241432136