Disrupted Immune Balance in Graves’ Disease: Evaluation of IL-35, CXCL10, and IL-4

Abstract

Graves’ Disease (GD) is driven by pathogenic TSH receptor antibodies (TRAb), yet the underlying imbalance between inflammatory (Th1/Th2) and regulatory (Treg) immune responses remains complex. Traditionally viewed as a Th2-mediated condition, it is also characterised by lymphocytic infiltration and inflammation in the thyroid and orbit. The study aims to investigate the immunological profile of patients with autoimmune hyperthyroidism by concurrently measuring IL-35, IL-4, and CXCL10 and to determine their diagnostic utility.

A case-control study with 90 participants—60 newly diagnosed, untreated GD patients and 30 healthy controls matched by age and sex—measured serum IL-4, CXCL10, and IL-35 levels using enzyme-linked immunosorbent assay (ELISA). Nonparametric tests, including the Mann-Whitney U test and ROC analysis, were used to evaluate the diagnostic performance of the biomarkers.

The study demonstrated that patients exhibited significantly elevated levels of IL-4 and CXCL10, with median values of approximately 575.20 ng/L and 193.40 ng/L, respectively, compared to healthy controls. Conversely, IL-35 levels were notably reduced in patients, with a median of 153.30 ng/L, compared to 471.30 ng/L in controls.

Our study reveals a distinct triple immune imbalance in GD patients, characterized by elevated CXCL10 and IL-4 levels and decreased IL-35 levels. These findings enhance understanding of GD's immune pathogenesis and suggest potential therapeutic targets.