Potential Predictor of Treatment Response in Chronic Spontaneous Urticaria Identified

Findings from a new study suggest that serum haptoglobin (HP) may serve as a useful prognostic biomarker for predicting treatment response and complete disease control in chronic spontaneous urticaria (CSU).¹

The researchers highlighted the potential of their findings, as identifying biomarkers that reflect disease activity and predict treatment outcomes remains a key unmet need in CSU management.² If validated in larger, multicenter studies, HP measurement could help clinicians stratify patients, anticipate treatment response, and move closer to biomarker-guided management of the disorder.¹

Marked by recurrent wheals, itching, and angioedema that persist for more than 6 weeks without an identifiable trigger, CSU is a mast cell–driven inflammatory skin disorder. Although histamine release from mast cells is central to symptom development, mounting evidence has pointed to broader immune dysregulation and systemic inflammation involvement in the disorder.

The new study, Clinical and Translational Allergy, included 124 patients with CSU and 57 healthy controls. Serum levels of HP, an acute-phase protein, and zonulin, a regulator of epithelial barrier integrity, were measured at baseline using enzyme-linked immunosorbent assays, and a subset of 62 patients was followed for 3 months after treatment initiation.

At baseline, serum HP levels were significantly higher in patients with CSU (median, 1145.1 μg/mL; IQR, 798.7-1415.7 μg/mL) compared with healthy controls (839.2 μg/mL; IQR, 499.6-1189.3 μg/mL; P = .001), indicating an association between CSU and systemic inflammatory activity. In contrast, zonulin levels did not differ between the 2 groups. Baseline HP showed weak but significant positive correlations with established inflammatory markers, including white blood cell count, complement C3, and C-reactive protein, while correlating negatively with disease duration and blood eosinophil percentage. The finding, explained the researchers, suggests that HP reflects an inflammatory dimension of CSU that is not fully captured by conventional biomarkers.

Importantly, HP levels changed dynamically with treatment. After 3 months, serum HP levels decreased significantly in treated patients (P < .001), whereas zonulin levels remained largely unchanged. The reduction in HP was more pronounced in patients who experienced clinically meaningful improvement, defined as a reduction of at least 12 points in the Urticaria Activity Score over 7 days. This pattern supports the potential role of HP as a marker of treatment-related inflammatory resolution.

Baseline HP levels were also associated with treatment outcomes. Patients who achieved complete urticaria control had significantly higher baseline HP concentrations than those with incomplete control. Receiver operating characteristic analysis identified a baseline HP threshold of 1249 μg/mL as the optimal cutoff for predicting complete control. After adjusting for confounding factors such as baseline disease severity, body mass index, and eosinophil percentage, a baseline HP level above this threshold remained an independent predictor of complete urticaria control, with more than 4-fold higher odds of achieving remission (adjusted odds ratio, 4.23; 95% CI, 1.16-15.46; P = .029).

“The predictive performance was comparable to those of other proposed prognostic markers such as the total IgE, CRP, or D‐dimer level,” noted the researchers.

In contrast, zonulin showed limited clinical utility in this cohort. Although baseline zonulin levels were modestly associated with poorer disease control, zonulin did not differ between patients and controls, did not change with treatment, and did not predict clinical response. These findings add to the inconsistent literature on zonulin in CSU and suggest that epithelial barrier dysfunction, while relevant in other allergic diseases, may play a less prominent or more heterogeneous role in CSU.

Several limitations were acknowledged by the researchers, including the single-center design, modest sample size, and heterogeneity of treatment regimens. In addition, the mechanistic role of HP in CSU remains unclear, and whether HP is merely a marker of inflammation or an active contributor to disease processes warrants further investigation.

References

1. Park K-W, Choi B, Moon D-H, Park S-M, Ye Y-M. Serum haptoglobin as a predictor of treatment response in patients with chronic spontaneous urticaria. Clin Trans Allergy. Published online January 7, 2026. doi:10.1002/clt2.70148

2. Ridge K, Ahmad R, Moran B, et al. Towards personalized therapy in chronic spontaneous urticaria: advancing from endotype to clinical response. Clin Exp Allergy. 2025;55(11):1070-1082. doi:10.1111/cea.70100