The Role of IgE in Allergic Disease

IgE-Immunoglobulin E

Immunoglobulin E (IgE) was discovered in the mid-1960s and has been proved to play an important role in type I allergic reactions. The conversion of antibody homotype to IgE may occur in nasal mucosa, bronchial tissue, and intestinal mucosa. Dendritic cells (DC) are present in the epithelium and upper lamina propria of respiratory tract, intestinal tract, and skin, which can capture allergens and promote T cells to polarize into allergic type II immune response. B cells are also important antigen presenting cells (APC) that initiate IgE hypersensitivity. The increased expression of Th2 cytokines such as IL-4 and IL-13 produced by mast cells and basophils in nasal mucosa can indirectly promote tissue mast cells to induce B cells to synthesize IgE, which leads to local synthesis of IgE by B cells. There is evidence that allergen-specific antibodies (non-IgE) in early life can regulate allergic sensitization. Maternal immunoglobulin is transferred to offspring during pregnancy and through breast milk, and maternal-specific allergen IgG seems to protect offspring from allergies. The recovery of immune tolerance after long-term allergen immunotherapy is related to the induction of local and systemic neutralizing antibodies against IgG and IgA.

IgE is structurally identical to other antibody classes, consisting of two identical light and heavy chains. Each chain consists of 110 amino acids that make up the "immunoglobulin structural domain", with disulfide bonds covalently connecting the light and heavy chains. Different from IgD, IgG and IgA with three constant region domains, the heavy chain is similar to the μ heavy chain of IgM in structure because it has four constant region domains (C_ε1-C_ε4). C_ε3 and C_ε4 domains are homologous to C_γ2 and C_γ3 domains of IgG antibody in sequence and quaternary structure. The difference between IgE and IgG lies in the position of its C_ε2 domain, which is inserted into the corresponding Fab-Fc hinge region of IgG. The two antigen binding sites are formed by pairing the variable regions of the light chain and the heavy chain. IgE bends asymmetrically at the C_ε2-3 linker, folds in on itself, and the two C_ε2 structural domains fold backward, almost touching the C_ε4 structural domain.

Immunoglobulin E is the core of type I immediate anaphylaxis. Several studies have shown that allotype conversion of antibodies beneficial to IgE occurs in the nasal and bronchial mucosa of allergic patients and in lymphoid tissue near the contact site of allergens. The concentrations of IgE antibody and Fc_εRI in target organs were increased, and the concentrations of atopic and allergic patients were more than ten times higher than those of non-atopic patients. IgE antibody has high affinity with Fc_εRI on the surface of mast cells and basophils.

Figure 1. IgE and its receptors
(Source: Shamji MH, et al. 2021)

IgE Mediated Reaction

• Role of IgE on mast and basophils responses

In the presence of IgE, both types of cells are activated by high affinity IgE receptors. Allergen-induced IgE cross-linking with Fc_εRIs on the surface of mast cells or basophils induces receptor aggregation and intracellular signal events, which leads to Ca²⁺-dependent release of formed mediators and the re-synthesis and secretion of lipid mediators and cytokines such as IL-4 and IL13. The concentration of allergen-specific IgE, IgE affinity and the ratio of allergen specificity to total IgE are the key factors to determine the release intensity of effector cells.

Figure 2. IgE-mediated Th2 and Mast cell/basophil activation and inhibitory effects of allergen-specific IgG and IgA as well as anti-IgE.
(Source: Shamji MH, et al. 2021)

• Role of IgE in Enhancing T-Cell Responses

Studies have shown that the specific IgE-allergen complex can significantly enhance the allergen-specific T cell response at low allergen concentrations. This IgE-mediated allergen presentation or promotion of allergen presentation involves the binding of IgE-allergen complex to CD23 on antigen-presenting B cells. It was also found that dendritic cells and monocytes in peripheral blood expressed high affinity IgE receptor (Fc_εRI) and activated allergen-specific T cells in an IgE-induced manner. In fact, these studies are related because the level of allergen in the respiratory tract is extremely low during natural exposure to allergens, and in this case of hypoallergen exposure, the presentation of allergens to T cells promoted by IgE activates T cells.

The binding of allergen-IgE complex to antigen-presenting cells depends on many parameters, such as the antigen specificity and affinity of IgE antibody, the expression level of receptor and the clonality of B cells. In addition, the complexity and affinity of IgE binding to multiple epitopes on allergens have been shown to be related to the promotion of T cell response. These results suggest that the number of IgE molecules bound to each allergen may play an important role in the formation and binding of this complex.

IgE ELISA Kits

IgE Antibodies

IgE Antigens