Immunoglobulin E (IgE) is one of the 5 classes of immunoglobulins, and is defined by the presence of the epsilon heavy chain. It is the most recently described immunoglobulin, having first been identified in 1966. IgE exists as a monomer, and is present in circulation at very low concentrations, approximately 300-fold lower than that of IgG. The physiologic role of IgE is not well characterized, although it is thought to be involved in defense against parasites, specifically helminthes.The function of IgE is also distinct from other immunoglobulins in that it induces activation of mast cells and basophils through the cell-surface receptor Fc epsilon RI. Fc epsilon RI is a high-affinity receptor specific for IgE present at a high density on tissue-resident mast cells and basophils. Because of this high-affinity interaction, almost all IgE produced by B cells is bound to mast cells or basophils, which explains the low concentration present in circulation. Cross-linking of the Fc epsilon RI-bound IgE leads to cellular activation, resulting in immediate release of preformed granular components (histamine and tryptase) and subsequent production of lipid mediators (prostaglandins and leukotrienes) and cytokines (interleukin-4 and interleukin-5).Elevated concentrations of IgE are generally thought of in the context of allergic disease. However, increases in the amount of circulating IgE can also be found in various other diseases, including primary immunodeficiencies, infections, inflammatory diseases, and malignancies. Total IgE measurements have limited utility for diagnostic evaluation of patients with suspected allergic disease, except for allergic bronchopulmonary aspergillosis (ABPA). ABPA is a hypersensitivity reaction against the fungi Aspergillus that occurs most frequently in patients with asthma or cystic fibrosis. An elevation of total IgE is part of the diagnostic criteria for ABPA, although the specific diagnostic concentration is dependent on certain patient characteristics.For patients with an established diagnosis of allergic disease, measurement of total IgE is necessary for identification of candidates for omalizumab (anti-IgE) therapy, and for determination of proper dosing. In addition to specific patient demographics and clinical presentations, candidates for omalizumab must have total IgE concentrations between 30 and 700 KU/L.