Immunoglobulin E
Immunoglobulin E (IgE) is a type of
IgE also has an essential role in
Although IgE is typically the least abundant isotype—
Discovery
IgE was simultaneously discovered in 1966 and 1967 by two independent groups:
Receptors
IgE primes the IgE-mediated allergic response by binding to Fc receptors found on the surface of mast cells and basophils. Fc receptors are also found on eosinophils, monocytes, macrophages and platelets in humans. There are two types of Fcε receptors:[citation needed]
- FcεRI(type I Fcε receptor), the high-affinity IgE receptor
- FcεRII(type II Fcε receptor), also known as CD23, the low-affinity IgE receptor
IgE can upregulate the expression of both types of Fcε receptors. FcεRI is expressed on mast cells, basophils, and the antigen-presenting dendritic cells in both mice and humans. Binding of antigens to IgE already bound by the FcεRI on mast cells causes cross-linking of the bound IgE and the aggregation of the underlying FcεRI, leading to degranulation (the release of mediators) and the secretion of several types of type 2 cytokines like interleukin (IL)-3 and stem cell factor (SCF), which both help the mast cells survive and accumulate in tissue, and IL-4, IL-5, IL-13, and IL-33, which in turn activate group 2-innate lymphoid cells (ILC2 or natural helper cells). Basophils share a common haemopoietic progenitor with mast cells; upon the cross-linking of their surface bound IgE by antigens, also release type 2 cytokines, including IL-4 and IL-13, and other inflammatory mediators. The low-affinity receptor (FcεRII) is always expressed on B cells; but IL-4 can induce its expression on the surfaces of macrophages, eosinophils, platelets, and some T cells.[16][17]
Function
Parasite hypothesis
The IgE isotype has co-evolved with basophils and mast cells in the defence against parasites like helminths (like Schistosoma) but may be also effective in bacterial infections.[18] Epidemiological research shows that IgE level is increased when infected by Schistosoma mansoni,[19] Necator americanus,[20] and nematodes[21] in humans. It is most likely beneficial in removal of hookworms from the lung.[citation needed]
Toxin hypothesis of allergic disease
In 1981 Margie Profet suggested that allergic reactions have evolved as a last line of defense to protect against venoms.[6] Although controversial at the time, new work supports some of Profet’s thoughts on the adaptive role of allergies as a defense against noxious toxins.[7]
In 2013 it emerged that IgE-antibodies play an essential role in acquired resistance to
Cancer
Although it is not yet well understood, IgE may play an important role in the immune system's recognition of cancer,[26] in which the stimulation of a strong cytotoxic response against cells displaying only small amounts of early cancer markers would be beneficial. If this were the case, anti-IgE treatments such as omalizumab (for allergies) might have some undesirable side effects. However, a recent study, which was performed based on pooled analysis using comprehensive data from 67 phase I to IV clinical trials of omalizumab in various indications, concluded that a causal relationship between omalizumab therapy and malignancy is unlikely.[27]
Role in disease
IgE that can specifically recognise an
IgE is known to be elevated in various autoimmune disorders such as
Regulation of IgE levels through control of B cell differentiation to antibody-secreting
Role in diagnosis
Diagnosis of allergy is most often done by reviewing a person's medical history and finding a positive result for the presence of allergen specific IgE when conducting a skin or blood test.[33] Specific IgE testing is the proven test for allergy detection; evidence does not show that indiscriminate IgE testing or testing for immunoglobulin G (IgG) can support allergy diagnosis.[34]
Drugs targeting the IgE pathway
Currently, allergic diseases and asthma are usually treated with one or more of the following drugs: (1)
IgE, the IgE synthesis pathway, and the IgE-mediated allergic/inflammatory pathway are all important targets in intervening with the pathological processes of allergy, asthma, and other IgE-mediated diseases. The B lymphocyte differentiation and maturation pathway that eventually generate IgE-secreting plasma cells go through the intermediate steps of IgE-expressing B lymphoblasts and involves the interaction with IgE-expressing memory B cells.
In 2002, researchers at the Randall Division of Cell and Molecular Biophysics determined the structure of IgE.[42] Understanding of this structure (which is atypical of other isotypes in that it is highly bent and asymmetric) and of the interaction of IgE with receptor FcεRI will enable development of a new generation of allergy drugs that seek to interfere with the IgE-receptor interaction. It may be possible to design treatments cheaper than monoclonal antibodies (for instance, small molecule drugs) that use a similar approach to inhibit binding of IgE to its receptor.[citation needed]
References
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- ^ Foley, James A. (25 October 2013). "Severe Allergies to Bee Stings may be Malfunctioning Evolutionary Response". Nature World News.
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