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

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.

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.

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.

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.

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.