Abstract
Allergy is an IgE-dependent type-I hypersensitivity reaction that can lead to life-threatening systemic symptoms such as anaphylaxis. In the pathogenesis of the allergic response, the common upstream event is the binding of allergens to specific IgE, inducing cross-linking of the high-affinity FcεRI on mast cells, triggering cellular degranulation and the release of histamine, proteases, lipids mediators, cytokines and chemokines with inflammatory activity. A number of novel therapeutic options to curb mast cell activation are in the pipeline for the treatment of severe allergies. In addition to anti-IgE therapy and allergen-specific immunotherapy, monoclonal antibodies targeted against several key Th2/alarmin cytokines (i.e. IL-4Rα, IL-33, TSLP), active modification of allergen-specific IgE (i.e. inhibitory compounds, monoclonal antibodies, de-sialylation), engagement of inhibitory receptors on mast cells and allergen-specific adjuvant vaccines, are new promising options to inhibit the uncontrolled release of mast cell mediators upon allergen exposure. In this review, we critically discuss the novel approaches targeting mast cells limiting allergic responses and the immunological mechanisms involved, with special interest on food allergy treatment.
Highlights
Nowadays, over 20% of the world population actively suffers from one or more allergies, among which approximately 10% is living with food allergy [1, 2]
The complex allergic reaction starts with the cross-linking of high-affinity immunoglobulin E (IgE) receptors (FcεRI) expressed on effector cells such as mast cells (MCs) and basophils by IgE– allergen complexes
E001 binds to IgE-Cε3 domains, promoting active disassociation of preno formed IgE-high-affinity IgE receptor (FcεRI) complexes via allosteric inhibition no formed IgE-FcεRI complexes via allosteric inhibition
Summary
Over 20% of the world population actively suffers from one or more allergies, among which approximately 10% is living with food allergy [1, 2]. Food allergies carry a high risk of developing systemic reactions upon allergen exposure, with 0.4–39.9% of allergic subjects experiencing at least one severe episode in their lifetime [3]. Anaphylaxis is a systemic reaction involving two or more organ systems, occurring shortly after the exposure to the culprit allergen. It manifests with a plethora of symptoms, including hives, angioedema, shortness of breath, vomiting, hypotension and cardiovascular collapse, which is potentially life-threatening and requires emergency treatment [4]. The complex allergic reaction starts with the cross-linking of high-affinity immunoglobulin E (IgE) receptors (FcεRI) expressed on effector cells such as mast cells (MCs) and basophils by IgE– allergen complexes. FcεRI engagement causes cell degranulation and release of preformed mediators, such as amines (histamine, polyamines), proteoglycans (heparin, chondroitin sulphates, serglycin), proteases (tryptase, chymase-1, cathepsin G, granzyme B, carboxypeptidase A3), lysosomal enzymes (bglucuronidase, b-hexosaminidase, arylsulfatase), newly formed lipid mediators (leukotrienes B4-C4, prostaglandin D2-E2), cytokines and chemokines (GM-CSF, IL-1b, IL-8, IL-13, MCP-1) [5, 6]
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