Haptoglobin Levels Predict Treatment Response in Chronic Spontaneous Urticaria

A simple blood test measuring levels of the protein haptoglobin may soon help doctors predict which patients with chronic spontaneous urticaria (CSU) are most likely to respond to treatment. New research suggests that elevated haptoglobin levels are associated with increased inflammation in CSU and can serve as a biomarker to guide clinical decision-making.

CSU, characterized by the spontaneous appearance of itchy welts (wheals) and swelling (angioedema) for more than six weeks without a clear trigger, affects an estimated 0.5% to 1% of the population. While antihistamines are often the first line of defense, not all patients experience adequate relief, highlighting the need for better ways to predict treatment response.

The study, published in Clinical and Translational Allergy on January 7, 2026, involved 124 patients with CSU and 57 healthy controls. Researchers found that patients with CSU had significantly higher levels of haptoglobin, an acute-phase protein produced by the liver, compared to those without the condition. This suggests a link between CSU and systemic inflammation.

Haptoglobin’s role in CSU isn’t fully understood. It’s an acute-phase protein, meaning its levels rise in response to inflammation. It also has antioxidant and immunomodulatory properties. The study authors noted that the correlation between haptoglobin and standard inflammatory markers like white blood cell count and C-reactive protein was relatively weak, suggesting it may reflect a distinct inflammatory pathway not typically captured by routine blood tests.

Crucially, the study showed that haptoglobin levels decreased in patients who responded to treatment over a three-month period. The most significant reductions were observed in patients who experienced a substantial improvement in their symptoms, as measured by a reduction of at least 12 points on the Urticaria Activity Score over 7 days. This dynamic change with treatment strengthens the idea that haptoglobin is a marker of inflammatory resolution.

The researchers identified a baseline haptoglobin cutoff of 1249 μg/mL as a potential predictor of complete disease control. Patients with levels above this threshold were more than four times as likely to achieve remission compared to those with lower levels (adjusted odds ratio, 4.23; 95% CI, 1.16-15.46; P = .029). This predictive performance was comparable to that of other biomarkers currently used in CSU, such as IgE, C-reactive protein, and D-dimer.

Another protein, zonulin, which is involved in regulating the intestinal barrier, did not show the same promise as a biomarker in this study. Zonulin levels did not differ between patients with CSU and healthy controls, nor did they change significantly with treatment. This suggests that disruptions in the epithelial barrier may not be a central feature of CSU, or that its role is more complex and variable.

While these findings are encouraging, the researchers acknowledge several limitations. The study was conducted at a single center and involved a relatively small sample size. The treatment regimens used were also varied, which could influence the results. Further research, including larger, multicenter studies, is needed to validate these findings and determine the optimal way to incorporate haptoglobin measurements into clinical practice.

“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,” the study authors wrote.

The identification of haptoglobin as a potential prognostic biomarker represents a step forward in the personalized management of CSU. By identifying patients who are more likely to respond to treatment, clinicians may be able to tailor therapies more effectively and improve outcomes for those living with this challenging condition.

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