The biology of IgE
- Jeff Stokes, MD, FAAAAI, FACAAI
Jeff Stokes, MD, FAAAAI, FACAAI
- Professor of Medicine
- Creighton University Medical Center
- Thomas B Casale, MD
Thomas B Casale, MD
- Executive Vice President, American Academy of Allergy Asthma and Immunology
- Professor of Medicine
- University of South Florida
The pathogenesis of many allergic diseases involves "allergic" antibody or immunoglobulin E (IgE) . This topic will review the structure, biology, and functions of IgE. A review of the role of IgE in allergic diseases and more general discussions of immunoglobulin structure and function are found elsewhere. (See "The relationship between IgE and allergic disease" and "Structure of immunoglobulins" and "Function and clinical applications of immunoglobulins".)
ROLES OF IgE
Immunoglobulin E (IgE) is important in defense against parasitic diseases, especially those caused by helminthes and some protozoa [2,3]. However, due in part to the redundancy of the immune system, low or absent levels of IgE do not predispose people to severe parasitic infections . IgE is not believed to play an important role in defense against bacterial infections, since it does not activate complement or participate in opsonization . IgE plays a key role in the pathogenesis of allergic diseases, especially mast cell/basophil activation, and in antigen presentation.
Immunoglobulin E (IgE) is one of five isotypes of human immunoglobulins, IgG, IgA, IgM, IgD, and IgE [6,7]. All immunoglobulins are composed of two light chains and two identical heavy chains (figure 1). The heavy chain differentiates the various immunoglobulin isotypes. The heavy chain in IgE is epsilon. IgE is a monomer and consists of four constant regions in contrast to other immunoglobulins that contain only three constant regions. Due to this extra region, the weight of IgE is 190 kDa compared with 150 kDa for IgG.
The C-epsilon-2 constant domain is unique to IgE, while the C-epsilon-3 region binds to the low- and high-affinity IgE receptor. Of note, the anti-IgE monoclonal antibody omalizumab also binds to the C-epsilon-3 region, so the binding of omalizumab to IgE decreases the amount of "free" IgE available for binding to IgE receptor-bearing cells, including mast cells and basophils (figure 1). (See "Anti-IgE therapy".)
Antibodies are produced by plasma cells. These cells are programmed to make immunoglobulin M (IgM) by default, but undergo "isotype-switching" to produce immunoglobulin E (IgE) with the same antigenic specificity under specific conditions. This process requires cell surface interactions between B and T cells, as well as soluble factors from various cell types [1,8-10]. During isotype-switching, genomic DNA is spliced and rejoined in class-switch recombination. (See "The humoral immune response", section on 'Cellular events in B cell activation' and "Immunoglobulin genetics".)
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- ROLES OF IgE
- Localized IgE production
- Regulation of synthesis
- IgE RECEPTORS
- High-affinity receptor
- Low-affinity receptor
- MEASUREMENT OF IgE
- Total IgE
- Allergen-specific IgE
- Affect of omalizumab
- IgE LEVELS
- Normal levels
- Childhood levels
- - Breastfeeding
- Decreased total IgE
- Increased total IgE
- - Atopic disorders
- - Immunodeficiencies
- - Infections
- - Inflammatory diseases
- - Neoplasms
- - Other disorders
- ANTI-IgE THERAPY