Gold induces a pseudo-allergic reaction via MRGPRX2 both in vitro and in vivo

The traditional mast cell (MC) degranulation pathway is mediated by crossing-linking of high-affinity IgE receptor (FcεRI), whereas a non-traditional, but analogous, pseudo-allergic way was recently reported to occur via Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2). Severe contact hypersensitivity to metallic gold, typically considered non-sensitizing, has been reported. However, whether gold induces IgE-independent allergy remains unclear. Therefore, this study assessed the effects of gold chloride (CA) on MC activation and its relation to MRGPRX2. Our data show that CA acted on MRGPRX2 to increase cellular calcium levels and induced the release of inflammatory mediators in vitro. Compared to Mrgprb2-knockout (KO) mice, CA dose-dependently induced passive cutaneous anaphylaxis (PCA) in wild-type (WT) mice. Furthermore, peritoneal mast cells (MPMCs) were extracted from WT and Mrgprb2-KO mice and stimulated by CA, but only MPMCs from WT mice could be activated. Our results suggest that CA-induced pseudo-allergic responses are MRGPRX2 dependent.