Serum Mrgprx2 and Substance P Levels: Biomarkers of Disease Activity, Not of Antihistamine Response in Chronic Spontaneous Urticaria: a Prospective Observational Study

Background : In chronic spontaneous urticaria (CSU), the role of Mas-related G protein-coupled receptor X2 (MRGPRX2) and substance P (SP) as biomarkers of disease severity and the antihistamine response remains unclear. The study aims to examine the correlations between serum MRGPRX2 and SP levels, disease severity, and antihistamine response in patients with CSU. Methods: This study included 120 CSU patients and 30 healthy controls. Based on the Urticaria Activity Score over 7 days (UAS7), the patients with CSU were divided into two categories: severe and non-severe. Severe CSU patients received 20 mg of bilastine, titrated up to 80 mg based on Urticaria Control Test (UCT) results at days 15, 30, and 60. Serum MRGPRX2 and SP levels were measured at baseline for all participants and after two months in severe CSU patients. The Kruskal-Wallis test and Dunn’s corrections were used to examine differences in multiple comparisons. Spearman’s correlation assessed the relationships between MRGPRX2 and SP levels and various clinical and laboratory parameters. Receiver Operating Characteristic (ROC) curves were created to identify the optimal serum levels of MRGPRX2 and SP for distinguishing severe CSU. Additionally, univariate and multivariate logistic regression analyses were conducted to identify risk factors associated with severe CSU. Results: Serum MRGPRX2 and SP levels were significantly higher in severe CSU patients than in non-severe patients (P<0.001 and P=0.01) but comparable to controls (P>0.05). These levels were positively correlated with the UAS7 (P<0.001 and P=0.01), with no correlation between MRGPRX2 and SP levels (P=0.28). MRGPRX2 ≥ 11.67 ng/mL and SP≥97.66 pg/mL were identified as independent risk factors for severe CSU (OR 48.21 95%CI 13.00–178.82; P< 0.001 and OR 3.19 95% CI 1.10–9.24, P=0.03). Among the severe CSU patients, the baseline MRGPRX2 and SP levels did not significantly differ across the antihistamine response groups (P>0.05). Serum MRGRPX2 levels remained consistent over time after antihistamine treatment (P=0.41), whereas serum SP concentrations significantly decreased (P<0.001). Conclusions : Serum MRGPRX2 and SP levels are associated with disease severity in CSU patients but do not predict antihistamine response in severe cases.