Elevated TFR1 is associated with inflammatory burden and ferroptosis in ulcerative colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal inflammation, oxidative stress, and iron metabolism dysregulation. Ferroptosis, an iron-dependent form of regulated cell death, may contribute to the pathogenesis of UC. Transferrin receptor 1 (TFR1), a key mediator of cellular iron uptake, links iron dysregulation to inflammation and ferroptosis; however, its clinical relevance in UC is not well defined.

Serum samples were collected from 83 patients with active UC and 80 age- and sex-matched healthy controls. Disease activity was assessed using the modified Mayo score. Serum TFR1, inflammatory cytokine, coagulation indices, oxidative stress marker, and ferroptosis-related antioxidant levels were measured. Correlations and receiver operating characteristic (ROC) curve analyses were performed to evaluate the associations and diagnostic performance.

Serum TFR1 levels were significantly higher in patients with UC than in controls (p < 0.001) and increased progressively with disease severity. TFR1 showed positive correlations with the Mayo score (r = 0.510), inflammatory markers, including C-reactive protein (CRP; r = 0.350), tumor necrosis factor-alpha (TNF-α; r = 0.406), interleukin-1 beta (IL-1β; r = 0.471), and interleukin-6 (IL-6; r = 0.432), coagulation parameters, including platelet count (r = 0.225), erythrocyte sedimentation rate (ESR; r = 0.451), and D-dimer (r = 0.447), serum iron (r = 0.267), and lipid peroxidation (r = 0.315), and negative correlations with the antioxidant defenses glutathione peroxidase 4 (GPX4; r = -0.236) and glutathione (GSH; r = -0.302). ROC analysis demonstrated that serum TFR1 distinguished patients with UC from controls, with an AUC of 0.795 at a cutoff of 4.8 ng/mL.

Elevated serum TFR1 levels are associated with UC severity, systemic inflammation, oxidative stress, and ferroptosis-related imbalance. These findings suggest that TFR1 is a potential biomarker for UC activity and highlight iron-driven ferroptosis as a promising therapeutic target, providing novel clinical insights into disease monitoring and management.