Serum Mas-related G protein-coupled receptor X2 concentration in drug-induced immediate hypersensitivity reactions

INTRODUCTION: Mas‑related G protein-coupled receptor X2 (MRGPRX2) has emerged as a mediator of mast cell activation in acute and chronic conditions. Exogenous ligands, such as neuromuscular blocking agents (NMBAs) and fluoroquinolones (FQs), can trigger MRGPRX2‑dependent activation and may augment immunoglobulin E (IgE)-mediated pathways. Although investigators have measured serum MRGPRX2 level in asthma, mastocytosis, and chronic urticaria, its role in immediate hypersensitivity reactions (IHRs) to FQs or NMBAs remains unclear. OBJECTIVES: We conducted this study to determine whether increased serum MRGPRX2 concentration is a risk factor for IHRs to NMBAs or FQs, and whether its concentration is related to reaction severity, causative agent, or serum tryptase. PATIENTS AND METHODS: We studied 43 patients with a history of IHRs to NMBAs or FQs, and compared them with 50 patients with IHR to Hymenoptera venom and 40 control individuals. The participants underwent a diagnostic evaluation that included skin testing, specific IgE measurement, and a basophil activation test when indicated. We measured serum MRGPRX2 level with an enzyme‑linked immunosorbent assay. RESULTS: Median serum MRGPRX2 concentrations with interquartile ranges for the drug‑induced reactions group, the Hymenoptera venom-induced reactions group, and the control group were 7.5 (3.73-15.64), 7 (3.96-10.62), and 5.89 (2.43-9.98) ng/ml, respectively (P = 0.32). Serum MRGPRX2 concentration showed no relationship with reaction severity, specific causative agents, or serum tryptase level. CONCLUSIONS: In this cohort, serum MRGPRX2 concentration was not a risk factor for the investigated drug- and venom‑induced IHRs. These findings do not support using serum MRGPRX2 level as a predictor of the reaction occurrence or severity in these settings.