Novel Approaches in the Inhibition of IgE-Induced Mast Cell Reactivity in Food Allergy (1)
Allergy is an IgE-dependent type-I hypersensitivity reaction that can lead to life-threatening systemic symptoms such as anaphylaxis.
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 (b- glucuronidase, 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).
IgE are mostly sequestered in peripheral tissues, with an average half-life estimated of 16–20 days in the skin versus 2–4 days in blood. By removing circulating IgE, the turnover between circulating and cell- bound allergen-specific IgE (sIgE) slowly declines, ultimately reducing the amount of sIgE bound on the cell surface and decreasing the likelihood of allergen-IgE cross-linking and allergen-specific effector cell responses.
