# Advances in MRGPRX2-mediated anaphylactoid reactions to traditional Chinese medicine injections

## TL;DR

This paper reviews how the MRGPRX2 receptor is central to allergic reactions from traditional Chinese medicine injections and explores methods to improve drug safety.

## Contribution

The paper introduces humanized mouse models and in vitro systems to study MRGPRX2-mediated reactions and proposes precision medication strategies based on genetic screening.

## Key findings

- MRGPRX2 is the key receptor mediating anaphylactoid reactions to TCMIs.
- Humanized mouse models and LAD2 cell systems enable accurate identification of sensitizing compounds.
- MRGPRX2 genetic polymorphisms and race influence reaction sensitivity and drug safety.

## Abstract

Traditional Chinese medicine injections (TCMIs) play an irreplaceable role in emergency treatment because of their rapid onset and high bioavailability. However, the incidence of non-IgE-mediated anaphylactoid reactions induced by TCMIs is high, accounting for the majority of acute allergic reactions, and posing a serious threat to clinical drug safety. Previous studies have identified the human Mas-related G protein-coupled receptor X2 (MRGPRX2) as the key receptor that mediates these reactions. This review discusses the crucial role of the mast cell surface receptor MRGPRX2 in TCMI-induced anaphylactoid reactions. Regarding research methodologies, approaches utilizing CRISPR/Cas9 technology or hematopoietic stem cell transplantation to construct humanized MRGPRX2 mouse models have been summarized. These models effectively addressed the issue of false negatives caused by species variation. Furthermore, an in vitro screening system based on LAD2 cells and the HEK293 overexpression system is described. Combined with calcium influx assays and histamine release measurements, this system enables precise identification of sensitizing bioactive compounds. Clinical studies indicate that MRGPRX2 polymorphisms and racial differences can affect receptor function, potentially altering sensitivity to TCMI-induced anaphylactoid reactions. Optimization strategies have been proposed based on underlying mechanisms, including the implementation of risk-stratified precision medication regimens guided by MRGPRX2 genetic screening. In summary, elucidating MRGPRX2 mechanisms, constructing relevant models, and developing intervention strategies provides a solid scientific foundation for enhancing TCMI safety, offering insights into reducing the risk of clinical anaphylactoid reactions.

Diagram showing anaphylactoid reaction pathways initiated by gene polymorphism 185A>G, involving compounds like salvianolic acid C, baicalin, and sinomenine. MRGPRX2 receptor activation increases calcium, cAMP, and MAPK pathways, causing mediator release like histamine, IL-6, and TNF-α. Symptoms include itchy skin, erythema, and dyspnea. Cationic liposome-encapsulated components like rosmarinic acid and quercetin are intervention strategies. Genetic screening can identify high, intermediate, and low risks. Includes LAD2 cell calcium flux assay and CRISPR/Cas9 editing model with a mouse, indicating research pathways. Frequency in the Asian population is noted as ten percent.