Serum free fatty acid profiles as novel biomarkers for disease activity in Graves' orbitopathy

Graves' orbitopathy (GO) lacks reliable serum biomarkers for objectively evaluating disease activity and severity. In this cross-sectional study, we aimed to investigate alterations in serum free fatty acid (FFA) profiles in GO and assess their potential as novel biomarkers.

We enrolled 60 patients with GO classified by Clinical Activity Score (CAS) and EUGOGO severity. Serum levels of 15 FFAs were measured. Principal component analysis (PCA) visualized group separations. Multivariable logistic regression, adjusted for age, sex, BMI, smoking, TRAb, identified independent predictors. Diagnostic performance was evaluated via ROC analysis, and clinical utility by decision curve analysis (DCA).

PCA showed clear separation between active and inactive GO. Active or moderate-to-severe disease was associated with significantly reduced anti-inflammatory FFAs, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), stearidonic acid (FFA18:4), total ω-3, and a lower EPA/AA ratio. After adjustment, decreased EPA/AA ratio (OR = 0.198, 95% CI: 0.051-0.760, p = 0.018) and FFA18:4 (OR = 0.667, 95% CI: 0.464-0.959, p = 0.029) were independent risk factors for active GO. The EPA/AA ratio discriminated active GO with an AUC of 0.847. DCA indicated its strong net clinical benefit across threshold probabilities.

GO exhibits a distinct serum FFA profile marked by reduced anti-inflammatory fatty acids. The EPA/AA ratio represents a robust, independent biomarker for GO activity, showing great potential for objective clinical assessment and guiding targeted therapy.