Immunoglobulin E

Source: Wikipedia, the free encyclopedia.
(Redirected from
IgE
)
The structure of the IgE antibody
The role of mast cells in the development of allergy.
Degranulation processes 1: antigen; 2: IgE antibody; 3: FcεRI receptor; 4: preformed mediators (histamine, proteases, chemokines, heparin); 5: granules; 6: mast cell; 7: newly formed mediators (prostaglandins, leukotrienes, thromboxanes, PAF)

Immunoglobulin E (IgE) is a type of

parasites such as Plasmodium falciparum.[5] IgE may have evolved as a defense to protect against venoms.[6][7][8]

IgE also has an essential role in

anaphylactic reactions to drugs, bee stings, and antigen preparations used in desensitization immunotherapy
.

Although IgE is typically the least abundant isotype—

adaptive immune response—it is capable of triggering anaphylaxis, one of the most rapid and severe immunological reactions.[11]

Discovery

IgE was simultaneously discovered in 1966 and 1967 by two independent groups:

Gunnar Johansson and Hans Bennich [sv] in Uppsala, Sweden.[14] Their joint paper was published in April 1969.[15]

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

Th2 immune responses, associated with production of IgE antibodies, which may "increase the resistance of mice to challenge with potentially lethal doses".[25]

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

hyper-IgE syndrome). However, this may not be a requirement for symptoms to occur as has been seen in asthmatics with normal IgE levels in their blood—recent research has shown that IgE production can occur locally in the nasal mucosa.[28]

IgE that can specifically recognise an

eczema, increased mucus secretion in allergic rhinitis, and increased vascular permeability, it is presumed, to allow other immune cells to gain access to tissues, but which can lead to a potentially fatal drop in blood pressure as in anaphylaxis.[citation needed
]

IgE is known to be elevated in various autoimmune disorders such as

SLE, rheumatoid arthritis (RA), and psoriasis, and is theorized to be of pathogenetic importance in SLE and RA by eliciting a hypersensitivity reaction.[29][30]

Regulation of IgE levels through control of B cell differentiation to antibody-secreting

T helper cells, causing the perpetuation of a Th2 response, one of the hallmarks of which is the production of more antibodies.[32]

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)

bronchodilators, which relax smooth muscle of constricted airway in asthma, or (4) mast cell stabilizers, which inhibit the degranulation of mast cells that is normally triggered by IgE-binding at FcεRI. Long-term uses of systemic corticosteroids are known to cause many serious side effects and are advisable to avoid, if alternative therapies are available.[citation needed
]

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.

antihistamines. In the second approach, antibodies specific for a domain of 52 amino acid residues, referred to as CεmX or M1’ (M1 prime), present only on human mIgE on B cells and not on free, soluble IgE, have been prepared and are under clinical development for the treatment of allergy and asthma.[38][39] An anti-M1’ humanized antibody, quilizumab, is in phase IIb clinical trial.[40][41]

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

  1. ^ "Antibody structure". Archived from the original on September 6, 2008.
  2. S2CID 24519249
    .
  3. .
  4. .
  5. .
  6. ^ .
  7. ^ .
  8. ^ .
  9. .
  10. .
  11. .
  12. .
  13. .
  14. .
  15. . Retrieved 2016-02-29.
  16. .
  17. .
  18. .
  19. .
  20. .
  21. .
  22. .
  23. ^ Sharlach, Molly (24 October 2013). "Bee sting allergy could be a defense response gone haywire, scientists say". Stanford Medicine News Center. Retrieved 20 November 2019.
  24. ^ Foley, James A. (25 October 2013). "Severe Allergies to Bee Stings may be Malfunctioning Evolutionary Response". Nature World News.
  25. PMID 26210895
    .
  26. .
  27. .
  28. .
  29. .
  30. .
  31. .
  32. .
  33. .
  34. ^ American Academy of Allergy, Asthma, and Immunology. "Five Things Physicians and Patients Should Question" (PDF). Choosing Wisely: An Initiative of the ABIM Foundation. Archived from the original (PDF) on November 3, 2012. Retrieved August 14, 2012.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  35. PMID 17383539
    .
  36. ^ "Novartis announces Xolair® approved in EU as first and only licensed therapy for chronic spontaneous urticaria (CSU) patients unresponsive to antihistamines". Novartis. 2014-03-06. Archived from the original on 2014-12-18. Retrieved 2014-12-04.
  37. ^ "Novartis announces US FDA approval of Xolair® for chronic idiopathic urticaria (CIU)". Novartis. 2014-03-21. Archived from the original on 2014-12-03. Retrieved 2014-12-04.
  38. PMID 20083663
    .
  39. .
  40. ^ "MEMP1972A". ClinicalTrials.gov. U.S. National Institutes of Health. Retrieved 2014-12-04.
  41. S2CID 41593528
    .
  42. .
This page is based on the copyrighted Wikipedia article: IgE. Articles is available under the CC BY-SA 3.0 license; additional terms may apply.Privacy Policy