Anaphylaxis in Mastocytosis

Gülen, Theo; Elberink, Joanne N.G. Oude; Brockow, Knut

doi:10.1007/978-3-030-27820-5_9

Cited by 2 publications

(1 citation statement)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the gene mutations described that might correlate with anaphylaxis severity, notably, the D816V activating mutation in KIT is the most consistent, confirmed by recent data from the European Anaphylaxis Registry [ 138 ]. In more than 95% of patients, the KIT activating mutation D816V is identified as the underlying cause of mastocytosis, the clonal expansion of mast cells is found as the basis of the onset and severity of allergic reactions [ 139 ]. Recently, the aberrant KIT D816V signal was associated with enhanced STAT5 phosphorylation and activity that contributes to an increase in IL-6 serum levels and a higher percentage of IL-6 positive mast cells, which associates with disease severity and progression [ 89 ].…”

Section: Host Genetic Factors or Mutations Related To Anaphylaxismentioning

confidence: 99%

Anaphylaxis: Focus on Transcription Factor Activity

Guo

Proaño-Pérez

Muñoz-Cano

et al. 2021

IJMS

View full text Add to dashboard Cite

Anaphylaxis is a severe allergic reaction, rapid in onset, and can lead to fatal consequences if not promptly treated. The incidence of anaphylaxis has risen at an alarming rate in past decades and continues to rise. Therefore, there is a general interest in understanding the molecular mechanism that leads to an exacerbated response. The main effector cells are mast cells, commonly triggered by stimuli that involve the IgE-dependent or IgE-independent pathway. These signaling pathways converge in the release of proinflammatory mediators, such as histamine, tryptases, prostaglandins, etc., in minutes. The action and cell targets of these proinflammatory mediators are linked to the pathophysiologic consequences observed in this severe allergic reaction. While many molecules are involved in cellular regulation, the expression and regulation of transcription factors involved in the synthesis of proinflammatory mediators and secretory granule homeostasis are of special interest, due to their ability to control gene expression and change phenotype, and they may be key in the severity of the entire reaction. In this review, we will describe our current understanding of the pathophysiology of human anaphylaxis, focusing on the transcription factors’ contributions to this systemic hypersensitivity reaction. Host mutation in transcription factor expression, or deregulation of their activity in an anaphylaxis context, will be updated. So far, the risk of anaphylaxis is unpredictable thus, increasing our knowledge of the molecular mechanism that leads and regulates mast cell activity will enable us to improve our understanding of how anaphylaxis can be prevented or treated.

show abstract

Section: Host Genetic Factors or Mutations Related To Anaphylaxismentioning

confidence: 99%

Anaphylaxis: Focus on Transcription Factor Activity

Guo

Proaño-Pérez

Muñoz-Cano

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

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

et al. 2021

View full text Add to dashboard Cite

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.

show abstract

Anaphylaxis in Mastocytosis

Cited by 2 publications

References 66 publications

Anaphylaxis: Focus on Transcription Factor Activity

Anaphylaxis: Focus on Transcription Factor Activity

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

Contact Info

Product

Resources

About