Abstract
BACKGROUND: Chronic spontaneous urticaria (CSU) is a mast cell-driven disease associated with systemic inflammation and altered immune responses. Haptoglobin (HP), an acute-phase glycoprotein, exhibits antioxidative and immunomodulatory properties, while zonulin, the precursor of HP-2, regulates epithelial barrier integrity. We investigated the clinical relevance of serum HP and zonulin in CSU and their association with treatment outcomes. METHODS: Serum HP and zonulin levels were measured by ELISA in 124 CSU patients and 57 healthy controls (HCs). In 62 CSU patients, follow-up samples were obtained after 3 months of treatment. Clinical outcomes included the urticaria activity score over 7 days (UAS7) and the urticaria control test (UCT). RESULTS: Serum HP levels were significantly higher in CSU patients than in HCs (median 1145.1 vs. 839.2 μg/mL, p < 0.001), whereas zonulin levels did not differ. HP correlated positively, but weakly, with the white blood cell count, C3 and C-reactive protein (all rho ≈ 0.2), and negatively with disease duration and eosinophil percentage. Zonulin correlated negatively with UCT scores but not with HP. After treatment, HP decreased significantly (p < 0.001), with greater reductions in patients showing a ≥ 12-point improvement on the UAS7. Baseline HP was higher in patients who achieved complete control (UCT = 16) than others (p = 0.017). ROC analysis identified baseline HP ≥ 1249 μg/mL as an optimal cutoff, confirmed as an independent predictor of complete control (odds ratio = 4.23, p = 0.029). CONCLUSION: Serum HP is elevated in CSU patients, decreases with treatment, and independently predicts complete urticaria control. HP may serve as a potentially prognostic biomarker for CSU.