IgE Signaling

IgE, one of the five classes of human antibodies (also called immunoglobulins), were shown to be the specific proteins that induce allergic diseases such as allergic asthma, severe food allergies and hay fever (allergic rhinitis) over 40 years ago. About 40% of people are genetically programmed to make IgE antibodies to a variety of inhaled and ingested proteins such as pollens, animal danders and a limited number of foods, such as peanut. Once produced, IgE binds to high affinity IgE receptors (FcεRIs) on mast cells and basophils, serving as the allergen trigger for those cells and resulting allergic reactions.

An allergic reaction begins when exposure to an allergen cross-links two or more IgEs bound to FcεRIs on mast cells and basophils. The cross-linking of the IgE-FcεRI complexes on the outside of these cells drives the activation of well-studied cascades of internal signaling molecules called kinases that result in the cells releasing a host of chemicals such as histamine and leukotrienes. It is the release of these chemical mediators that results in the allergic manifestations of anaphylaxis, severe food allergy, allergic asthma and/or allergic rhinitis, depending on the organ system(s) involved.

Allergen-induced IgE-FcεRI complex cross-linking causes not only the early-phase allergic response, including anaphylaxis, that occurs in minutes, but also the delayed late-phase response that occurs hours later following the recruitment of cells that release other pro-inflammatory molecules.