Antibody or Anybody? Considering the Role of MRGPRX2 in Acute Drug-Induced Anaphylaxis and as a Therapeutic Target

Acute anaphylaxis to small molecule drugs is largely considered to be antibody-mediated with immunogloblin E (IgE) and mast cell activation being key. More recently, a role for drug-reactive immunoglobulin G (IgG) with neutrophil activation has also been suggested, at least in reactions to neuromusc...

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Autores principales:	Graham A. Mackay, Nithya A. Fernandopulle, Jie Ding, Jeremy McComish, Paul F. Soeding
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	anaphylaxis mast cells drug hypersensitivity MRGPRX2 IgE (immunoglobulin E) Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/902754596de042d29c3d9292309981a4
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spelling	oai:doaj.org-article:902754596de042d29c3d9292309981a42021-11-19T05:32:44ZAntibody or Anybody? Considering the Role of MRGPRX2 in Acute Drug-Induced Anaphylaxis and as a Therapeutic Target1664-322410.3389/fimmu.2021.688930https://doaj.org/article/902754596de042d29c3d9292309981a42021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.688930/fullhttps://doaj.org/toc/1664-3224Acute anaphylaxis to small molecule drugs is largely considered to be antibody-mediated with immunogloblin E (IgE) and mast cell activation being key. More recently, a role for drug-reactive immunoglobulin G (IgG) with neutrophil activation has also been suggested, at least in reactions to neuromuscular blocking agents (NMBAs). However, the mast cell receptor MRGPRX2 has also been highlighted as a possible triggering mechanism in acute anaphylaxis to many clinically used drugs. Significantly, MRGPRX2 activation is not dependent upon the presence of drug-recognising antibody. Given the reasonable assumption that MRGPRX2 is expressed in all individuals, the corollary of this is that in theory, anybody could respond detrimentally to triggering drugs (recently suggested to be around 20% of a drug-like compound library). But this clearly is not the case, as the incidence of acute drug-induced anaphylaxis is very low. In this mini-review we consider antibody-dependent and -independent mechanisms of mast cell activation by small molecule drugs with a focus on the MRGPRX2 pathway. Moreover, as a juxtaposition to these adverse drug actions, we consider how increased understanding of the role of MRGPRX2 in anaphylaxis is important for future drug development and can complement exploration of this receptor as a drug target in broader clinical settings.Graham A. MackayNithya A. FernandopulleJie DingJeremy McComishPaul F. SoedingPaul F. SoedingFrontiers Media S.A.articleanaphylaxismast cellsdrug hypersensitivityMRGPRX2IgE (immunoglobulin E)Immunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	anaphylaxis mast cells drug hypersensitivity MRGPRX2 IgE (immunoglobulin E) Immunologic diseases. Allergy RC581-607
spellingShingle	anaphylaxis mast cells drug hypersensitivity MRGPRX2 IgE (immunoglobulin E) Immunologic diseases. Allergy RC581-607 Graham A. Mackay Nithya A. Fernandopulle Jie Ding Jeremy McComish Paul F. Soeding Paul F. Soeding Antibody or Anybody? Considering the Role of MRGPRX2 in Acute Drug-Induced Anaphylaxis and as a Therapeutic Target
description	Acute anaphylaxis to small molecule drugs is largely considered to be antibody-mediated with immunogloblin E (IgE) and mast cell activation being key. More recently, a role for drug-reactive immunoglobulin G (IgG) with neutrophil activation has also been suggested, at least in reactions to neuromuscular blocking agents (NMBAs). However, the mast cell receptor MRGPRX2 has also been highlighted as a possible triggering mechanism in acute anaphylaxis to many clinically used drugs. Significantly, MRGPRX2 activation is not dependent upon the presence of drug-recognising antibody. Given the reasonable assumption that MRGPRX2 is expressed in all individuals, the corollary of this is that in theory, anybody could respond detrimentally to triggering drugs (recently suggested to be around 20% of a drug-like compound library). But this clearly is not the case, as the incidence of acute drug-induced anaphylaxis is very low. In this mini-review we consider antibody-dependent and -independent mechanisms of mast cell activation by small molecule drugs with a focus on the MRGPRX2 pathway. Moreover, as a juxtaposition to these adverse drug actions, we consider how increased understanding of the role of MRGPRX2 in anaphylaxis is important for future drug development and can complement exploration of this receptor as a drug target in broader clinical settings.
format	article
author	Graham A. Mackay Nithya A. Fernandopulle Jie Ding Jeremy McComish Paul F. Soeding Paul F. Soeding
author_facet	Graham A. Mackay Nithya A. Fernandopulle Jie Ding Jeremy McComish Paul F. Soeding Paul F. Soeding
author_sort	Graham A. Mackay
title	Antibody or Anybody? Considering the Role of MRGPRX2 in Acute Drug-Induced Anaphylaxis and as a Therapeutic Target
title_short	Antibody or Anybody? Considering the Role of MRGPRX2 in Acute Drug-Induced Anaphylaxis and as a Therapeutic Target
title_full	Antibody or Anybody? Considering the Role of MRGPRX2 in Acute Drug-Induced Anaphylaxis and as a Therapeutic Target
title_fullStr	Antibody or Anybody? Considering the Role of MRGPRX2 in Acute Drug-Induced Anaphylaxis and as a Therapeutic Target
title_full_unstemmed	Antibody or Anybody? Considering the Role of MRGPRX2 in Acute Drug-Induced Anaphylaxis and as a Therapeutic Target
title_sort	antibody or anybody? considering the role of mrgprx2 in acute drug-induced anaphylaxis and as a therapeutic target
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/902754596de042d29c3d9292309981a4
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Antibody or Anybody? Considering the Role of MRGPRX2 in Acute Drug-Induced Anaphylaxis and as a Therapeutic Target

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