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Immunoglobulin E is 1 of the 5 classes of immunoglobulins (IgM, IgG, IgD, IgA, IgE). IgE has a unique chemical structure and various physiological functions, such as type I hypersensitivity reactions, parasitic infections, autoimmune processes, and venom protection.[1] It was the last of the immunoglobulin family to be discovered. Since then, it has spurred vast research to characterize its biochemistry and role in disease processes. Technological advancements have also been used to evaluate patient IgE levels and new pharmacological therapies that may inhibit its function altogether.[2] This topic provides an overview of the biochemical structure and function of IgE, along with examples of its clinical implications.

The role of IgE is central in allergy sensitization and atopic disorders such as allergic rhinitis, asthma, and atopic dermatitis. These disorders ultimately manifest due to type I hypersensitivity reactions involving IgE and other immune cells, which produce the clinical symptoms seen in those disorders. It starts with initial exposure to an antigen or allergen, which is taken up and processed by a dendritic cell or macrophage, which then presents the antigen to a T cell. In the presence of cytokine mediators IL-4 and IL-13, these T-cells are induced to differentiate into TH2 helper T-cells capable of presenting the antigen to B-cells.[6] The B cells then undergo class-switch recombination to produce Immunoglobulin E antibodies capable of binding the presented antigen at the "antigen binding site" of the Fab portion of the antibody. Once this initial sensitization to the antigen has occurred, more immunological events can ensure a more robust IgE response. The CD23 receptor on intestinal or airway epithelial cells can transport antigen-IgE complexes across the epithelium, binding Fc-epsilon-RI receptors on mast cells, macrophages, and other immune cells to promote inflammation, cytokine production, and local IgE production. Furthermore, via interaction with the CD23 receptor on B-cells and myeloid cells, a process known as FAP can occur.

The role of IgE is central in allergy sensitization and atopic disorders such as allergic rhinitis, asthma, and atopic dermatitis. These disorders ultimately manifest due to type I hypersensitivity reactions involving IgE and other immune cells, which produce the clinical symptoms seen in those disorders. It starts with initial exposure to an antigen or allergen, which is taken up and processed by a dendritic cell or macrophage, which then presents the antigen to a T cell. In the presence of cytokine mediators IL-4 and IL-13, these T-cells are induced to differentiate into TH2 helper T-cells capable of presenting the antigen to B-cells.[6] The B cells then undergo class-switch recombination to produce Immunoglobulin E antibodies capable of binding the presented antigen at the "antigen binding site" of the Fab portion of the antibody. Once this initial sensitization to the antigen has occurred, more immunological events can ensure a more robust IgE response. The CD23 receptor on intestinal or airway epithelial cells can transport antigen-IgE complexes across the epithelium, binding Fc-epsilon-RI receptors on mast cells, macrophages, and other immune cells to promote inflammation, cytokine production, and local IgE production. Furthermore, via interaction with the CD23 receptor on B-cells and myeloid cells, a process known as FAP can occur. FAP involves antigen-IgE complexes binding to CD23 receptors on B cells, which then present the peptides to T cells to facilitate further IgE antibody production.[7] This approach contrasts with the classical antigen presentation pathway described above. Instead of T-cells being the primary antigen-presenters to B-cells, it is now antigen-IgE complexes formed in the periphery that may or may not be related to the initial antigen. This has clinical importance because, via facilitated antigen presentation, B cells ultimately present a diverse array of peptides to T cells, enabling them to be cleared for further immunoglobulin production. In conclusion, this is a mechanism of epitope spreading, in which an antibody response to 1 antigen can trigger the production of antibodies against different antigens.[6] This may explain why individuals can develop allergies to multiple antigens, leading to a phenomenon known as "atopic march."[8] For example, a child could have atopic dermatitis and later in life develop asthma. In conclusion, facilitated antigen presentation produces a more robust immune response to a given antigenic exposure that could be responsible for sensitization to multiple unrelated antigens.

FAP involves antigen-IgE complexes binding to CD23 receptors on B cells, which then present the peptides to T cells to facilitate further IgE antibody production.[7] This approach contrasts with the classical antigen presentation pathway described above. Instead of T-cells being the primary antigen-presenters to B-cells, it is now antigen-IgE complexes formed in the periphery that may or may not be related to the initial antigen. This has clinical importance because, via facilitated antigen presentation, B cells ultimately present a diverse array of peptides to T cells, enabling them to be cleared for further immunoglobulin production. In conclusion, this is a mechanism of epitope spreading, in which an antibody response to 1 antigen can trigger the production of antibodies against different antigens.[6] This may explain why individuals can develop allergies to multiple antigens, leading to a phenomenon known as "atopic march."[8] For example, a child could have atopic dermatitis and later in life develop asthma. In conclusion, facilitated antigen presentation produces a more robust immune response to a given antigenic exposure that could be responsible for sensitization to multiple unrelated antigens. Once initial exposure to an antigen occurs and an immune response is activated, antigen-specific IgE remains bound to mast cells and basophils via the Fc-epsilon RI receptor. It has been shown that binding IgE to that receptor alone causes IgE-dependent upregulation of mast cell Fc-epsilon RI receptor expression, allowing these cells to bind more IgE antibodies.[6] Furthermore, it is essential to note that IgE has a short half-life in plasma, usually less than a day. However, IgE bound to a high-affinity receptor (Fc-epsilon RI) can remain attached to mast cells in tissues for weeks to months.[4] Later, upon re-exposure to a given antigen, crosslinking of adjacent Fc-epsilon RI-bound IgE antibodies occurs, binding the antigen and triggering subsequent aggregation of Fc-epsilon RI receptors. Once this happens and there is sufficient aggregation of these receptors with bound antigen, mast cells and basophils release preformed chemical mediators stored in cytoplasmic granules, such as histamine, serotonin, tryptase, prostaglandins, leukotrienes, and eosinophil or neutrophil chemotactic factors.[6]