Association Between Peripheral IL-2⁺Th1/CD4⁺Tregs Axis Imbalance and Dysthyroid Optic Neuropathy in Thyroid Eye...

Background/Objective: Dysthyroid Optic Neuropathy (DON) is a severe complication of Thyroid Eye Disease (TED) leading to irreversible visual impairment. Its pathogenesis remains unclear, and early predictive tools are lacking. The study aims to investigate peripheral immune characteristics associated with DON, focusing on the IL-2⁺Th1/CD4⁺Tregs axis. Methods: A retrospective study was conducted in 37 TED patients, including DON (n = 22) and non-DON (n = 15) groups. Peripheral blood immune cell subsets were quantified using flow cytometry. Clinical data and peripheral blood immune indicators including T cell subsets, B cell subsets, T helper (Th) cell subsets, and regulatory T (Treg) cells populations were analyzed. Correlation and logistic regression analyses were applied to evaluate associations between immune indicators and DON. Receiver operating characteristic (ROC) analysis was used to assess the discriminatory performance of candidate variables and exploratory combined models. Results: Patients with DON showed higher IL-2⁺Th1 levels and lower CD4⁺Tregs levels compared with non-DON patients, along with an increased IL-2⁺Th1/CD4⁺Tregs ratio. Age and clinical activity score also differed significantly between groups. The IL-2⁺Th1/CD4⁺Tregs axis showed significant alterations associated with DON. The exploratory logistic regression model combining immune and clinical indicators showed potential discriminatory ability in differentiating DON from non-DON patients. Conclusions: This study identifies an imbalance between IL-2⁺Th1 and CD4⁺Tregs as a potential immune signature associated with DON. Integration of immune and clinical features may provide an exploratory framework for risk stratification in TED. Further prospective studies with larger cohorts are warranted to validate these findings.