Mechanisms Governing Anaphylaxis: Inflammatory Cells, Mediators, Endothelial Gap Junctions and Beyond

Area of Science:

• Immunology and Allergy
• Pathophysiology of Severe Allergic Reactions

Background:

• Anaphylaxis is a life-threatening multisystem allergic reaction involving mast cell mediator release.
• Triggers include medications, foods, latex, exercise, hormones, and mast cell disorders.
• Novel syndromes like delayed red meat reactions and hereditary alpha-tryptasemia are emerging.

Purpose of the Study:

• To review the mechanisms underlying IgE-mediated anaphylaxis.
• To provide an overview of non-IgE-mediated reactions that mimic anaphylaxis.
• To highlight the potential for precision medicine approaches in managing anaphylaxis.

Main Methods:

• Review of existing literature on anaphylaxis pathophysiology and mediators.
• Analysis of traditional IgE-mediated pathways involving mast cells and basophils.
• Exploration of alternative pathways including IgG, complement, and contact system involvement.

Main Results:

• Mast cell degranulation releases mediators (histamine, tryptase, TNF-α, leukotrienes, PAF, VEGF) that increase vascular permeability.
• These mediators cause endothelial barrier dysfunction, leading to airway edema, hypovolemia, and distributive shock.
• Non-IgE mediated pathways can also manifest as anaphylaxis-like phenotypes.

Conclusions:

• Anaphylaxis involves complex mediator cascades affecting multiple organ systems.
• Understanding diverse endotypes of anaphylaxis is crucial for effective treatment.
• Classification of anaphylaxis subtypes may pave the way for precision medicine strategies.