Abstract

Allergic rhinitis (AR) is a prevalent inflammatory disorder located in the nasal tissues, imposing a substantial global disease burden. Current diagnostic methods detect allergic sensitization but lack the capacity to discriminate subgroups, limiting the precision of therapeutics. Serum levels of Mas-related G protein-coupled receptor X2 (MRGPRX2), elevated in allergic conditions, remain unvalidated as an AR biomarker. We hypothesized that serum MRGPRX2 serves as a novel diagnostic biomarker enabling subgroup-driven AR management. We enrolled 213 seasonal AR patients and 113 matched healthy controls at the hospital and quantified serum MRGPRX2 levels using an enzyme-linked immunosorbent assay. Diagnostic performance was evaluated using receiver operating characteristic curves, and binary logistic regression was used to estimate the odds ratio for AR risk. AR cases had higher MRGPRX2 levels (69.84 vs. 40.67 ng/mL, P < 0.001). Although the area under the curve (AUC) for MRGPRX2 (0.77) was lower than that of total IgE (0.85), it remained a significant predictor. At a cut-off of 39.11 ng/mL, the sensitivity was 85.45%. Furthermore, patients with severe AR exhibited significantly higher MRGPRX2 levels compared to those with mild/moderate AR ( P < 0.01). The correlation between serum MRGPRX2 and total IgE levels was weak ( r = 0.264, P < 0.001), revealing a distinct clinical subgroup characterized by low serum total IgE but elevated MRGPRX2 (14.08% of cohort). Thus, serum MRGPRX2 is a promising diagnostic biomarker for AR, capable of stratifying patients, particularly identifying an IgE-low/MRGPRX2-high subgroup. This putative subgroup may require alternative treatment approaches targeting MRGPRX2-mediated pathways.