MRGPRX2 Activation Causes Increased Skin Reactivity in Patients with Chronic Spontaneous Urticaria

Shtessel, Maria; Limjunyawong, Nathachit; Oliver, E; Chichester, Kristin L.; Gao, Li; Dong, Xinzhong; Saini, Sarbjit S.

doi:10.1016/j.jid.2020.06.030

Cited by 54 publications

(38 citation statements)

References 15 publications

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“…An example is provided below in the vancomycin section, in which bacterial infections appear to dramatically reduce systemic mast cell responses. On the other hand, patients with chronic spontaneous urticaria appear to have much stronger responses to MRGPRX2 agonists (26). This is an emerging topic and more research needs to be performed, but it is clear that comorbidities can have a profound influence on allergic-type reactions.…”

Section: Mrgprx2 Involvementmentioning

confidence: 99%

MRGPRX2 and Adverse Drug Reactions

McNeil

2021

Front. Immunol.

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Many adverse reactions to therapeutic drugs appear to be allergic in nature, and are thought to be triggered by patient-specific Immunoglobulin E (IgE) antibodies that recognize the drug molecules and form complexes with them that activate mast cells. However, in recent years another mechanism has been proposed, in which some drugs closely associated with allergic-type events can bypass the antibody-mediated pathway and trigger mast cell degranulation directly by activating a mast cell-specific receptor called Mas-related G protein-coupled receptor X2 (MRGPRX2). This would result in symptoms similar to IgE-mediated events, but would not require immune priming. This review will cover the frequency, severity, and dose-responsiveness of allergic-type events for several drugs shown to have MRGPRX2 agonist activity. Surprisingly, the analysis shows that mild-to-moderate events are far more common than currently appreciated. A comparison with plasma drug levels suggests that MRGPRX2 mediates many of these mild-to-moderate events. For some of these drugs, then, MRGPRX2 activation may be considered a regular and predictable feature after administration of high doses.

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Section: Mrgprx2 Involvementmentioning

confidence: 99%

MRGPRX2 and Adverse Drug Reactions

McNeil

2021

Front. Immunol.

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“…Recently, other MRGPRX2 ligands, such as rocuronium, have been shown to cause increased skin reactivity in CSU patients [ 75 ]. In other types of urticaria, such as vibratory urticaria, for example, other G protein-coupled mast cell receptors have induced MC activation through mechanical vibration [ 23 ].…”

Section: Prolonged Type-2 Inflammationmentioning

confidence: 99%

The Multifaceted Mas-Related G Protein-Coupled Receptor Member X2 in Allergic Diseases and Beyond

Quan

Sabaté‐Brescó

Guo

et al. 2021

IJMS

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Recent research on mast cell biology has turned its focus on MRGPRX2, a new member of the Mas-related G protein-coupled subfamily of receptors (Mrgprs), originally described in nociceptive neurons of the dorsal root ganglia. MRGPRX2, a member of this group, is present not only in neurons but also in mast cells (MCs), specifically, and potentially in other cells of the immune system, such as basophils and eosinophils. As emerging new functions for this receptor are studied, a variety of both natural and pharmacologic ligands are being uncovered, linked to the ability to induce receptor-mediated MC activation and degranulation. The diversity of these ligands, characterized in their human, mice, or rat homologues, seems to match that of the receptor’s interactions. Natural ligands include host defense peptides, basic molecules, and key neuropeptides such as substance P and vasointestinal peptide (known for their role in the transmission of pain and itch) as well as eosinophil granule-derived proteins. Exogenous ligands include MC secretagogues such as compound 48/80 and mastoparan, a component of bee wasp venom, and several peptidergic drugs, among which are members of the quinolone family, neuromuscular blocking agents, morphine, and vancomycin. These discoveries shed light on its capacity as a multifaceted participant in naturally occurring responses within immunity and neural stimulus perception, as in responses at the center of immune pathology. In host defense, the mice Mrgprb2 has been proven to aid mast cells in the detection of peptidic molecules from bacteria and in the release of peptides with antimicrobial activities and other immune mediators. There are several potential actions described for it in tissue homeostasis and repair. In the realm of pathologic response, there is evidence to suggest that this receptor is also involved in chronic inflammation. Furthermore, MRGPRX2 has been linked to the pathophysiology of non-IgE-mediated immediate hypersensitivity drug reactions. Different studies have shown its possible role in other allergic diseases as well, such as asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria. In this review, we sought to cover its function in physiologic processes and responses, as well as in allergic and nonallergic immune disease.

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“…These include the complement C5a receptor (C5aR, CD88), to which the anaphylatoxin C5a binds, and the Mas-related G protein-coupled receptor X2 (MRGPRX2), both preferentially expressed by the skin MCs. [31][32][33][34] MRGPRX2 is a receptor that is activated by substance P, major basic protein, and eosinophil peroxidase and by various external triggers. 35 A small group of MC receptors mediates inhibitory signals.…”

Section: Definition and Burdenmentioning

confidence: 99%

EAACI Biologicals Guidelines—Omalizumab for the treatment of chronic spontaneous urticaria in adults and in the paediatric population 12–17 years old

Agache

Akdiş

Brockow

et al. 2021

Allergy

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Chronic spontaneous urticaria (CSU) imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity and insufficient efficacy of classical drugs such as H 1 R-antihistamines. Better understanding of the mechanisms has enabled a stratified approach to the management of CSU, supporting the use of targeted treatment with omalizumab. However, many practical issues including selection of responders, the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based) and its cost-effectiveness still require further clarification. The EAACI Guidelines on the use of omalizumab in CSU follow the GRADE approach in formulating recommendations for each outcome. In addition, future therapeutic approaches and perspectives as well as research priorities are discussed.

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MRGPRX2 Activation Causes Increased Skin Reactivity in Patients with Chronic Spontaneous Urticaria

Cited by 54 publications

References 15 publications

MRGPRX2 and Adverse Drug Reactions

MRGPRX2 and Adverse Drug Reactions

The Multifaceted Mas-Related G Protein-Coupled Receptor Member X2 in Allergic Diseases and Beyond

EAACI Biologicals Guidelines—Omalizumab for the treatment of chronic spontaneous urticaria in adults and in the paediatric population 12–17 years old

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