Plasma MRGPRX2 Correlates with Severity of Artemisia-Induced Allergic Rhinitis, Particularly in IgE-Negative Patients: A Cross-Sectional Study

Purpose: Mas-related G-protein-coupled receptor member X2 (MRGPRX2) is a key receptor in mast cell activation and plays a critical role in mediating pseudo-allergic reactions. However, its role in allergic rhinitis (AR) remains poorly understood. Therefore, we investigated the correlation between plasma MRGPRX2 and symptoms in AR patients. Patients and Methods: A total of 116 patients with typical AR symptoms and positive skin prick test results and 100 healthy controls were recruited. Plasma MRGPRX2, total and specific IgE, and histamine were measured. AR patients who tested negative for both total IgE and sIgE were defined as IgE-negative. Symptom severity was evaluated using a questionnaire combining the Total Nasal Symptom Score (TNSS) and the Visual Analog Scale (VAS). TNSS assessed nasal (sneezing, rhinorrhea, congestion, itching), each scored from 0 (none) to 3 (severe). The VAS ranged from 0 cm (no symptoms) to 10 cm (most severe). Results: Plasma MRGPRX2 levels were significantly elevated in patients with AR compared with healthy controls (P<0.001) and demonstrated good discriminative performance (AUC=0.92, P<0.001). Moreover, patients with moderate to severe AR had significantly higher plasma MRGPRX2 levels than those with mild AR (P<0.001). A significant positive correlation was also observed between plasma MRGPRX2 levels and VAS scores (ρ=0.37, P<0.001). This correlation was stronger in the IgE-negative AR group (ρ=0.61, P<0.001) compared with the IgE-positive group (ρ=0.25, P=0.027) (Z=2.25, P=0.024). Notably, plasma MRGPRX2 levels were positively correlated with TNSS only in IgE-negative AR patients (ρ=0.38, P=0.016), whereas no significant correlation was observed in the IgE-positive group (ρ=0.17, P=0.238). Conclusion: Plasma MRGPRX2 levels are elevated in patients with AR and are positively correlated with disease symptoms, particularly in IgE-negative cases. MRGPRX2 may serve as a novel biomarker to improve the classification and management of AR, especially in patients exhibiting allergic symptoms despite clinically insignificant IgE levels.