Immunoglobulin E (IgE) is an antibody subclass (known as "isotypes"), found only in mammals. Although IgE is typically the least abundant isotype - blood serum IgE levels in a normal ("non-atopic") individual are ~150ng/ml, compared to 10mg/ml for the IgGs (the isotypes responsible for most of the classical adaptive immune response) - it is capable of triggering the most powerful immune reactions. Most of our knowledge of IgE has come from research into the mechanism of a form of allergy known as type 1 hypersensitivity (1). Schematic of antibody binding to an antigen An antibody is a protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... Orders Subclass Monotremata Monotremata Subclass Marsupialia Didelphimorphia Paucituberculata Microbiotheria Dasyuromorphia Peramelemorphia Notoryctemorphia Diprotodontia Subclass Placentalia Xenarthra Dermoptera Desmostylia Scandentia Primates Rodentia Lagomorpha Insectivora Chiroptera Pholidota Carnivora Perissodactyla Artiodactyla Cetacea Afrosoricida Macroscelidea Tubulidentata Hyracoidea Proboscidea Sirenia The mammals are the class of vertebrate animals primarily characterized by the presence of mammary... In medicine, the atopic syndrome is the clustering of eczema, allergic conjunctivitis, allergic rhinitis and asthma in certain individuals. ... An allergy or Type I hypersensitivity is an immune system malfunction whereby a persons body is hypersensitised to react immunologically to typically nonimmunogenic substances. ... Hypersensitivity is an immune response that damages the bodys own tissues. ...

Physiology

IgE's role in allergy is presumably inappropriate — why would a systemic anaphylactic reaction to a harmless substance be biologically useful? There is much speculation into what positive aspects IgE has, and so far, circumstantial evidence in animal models and statistical population trends have hinted that IgE may be beneficial in fighting gut parasites such as Schistosoma mansoni, but this has not been conclusively proven in humans. A parasite is an organism that lives in or on the living tissue of a host organism at the expense of it. ... Binomial name Schistosoma mansoni Sambon, 1907 Schistosoma mansoni is an important human parasite. ...

Although it is not yet well understood, IgE may play an important role in the immune system’s recognition of cancer (4), in which the stimulation of a strong cytotoxic response against cells displaying only small amounts of early cancer markers would be beneficial. Of course, if this were the case, anti-IgE treatments such as Omalizumab might have some unforeseen side effects. When normal cells are damaged beyond repair, they are eliminated by apoptosis. ...

Role in disease

Atopic individuals (people who suffer from true IgE-mediated allergies) can have up to 10 times the normal level of IgE in their blood (as do sufferers of 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, heretically without the involvement of lymphoid tissue (2). Incredibly, the implications of this are still not fully appreciated by the medical community, so the importance of IgE in allergy is often underestimated. In medicine, the atopic syndrome is the clustering of eczema, allergic conjunctivitis, allergic rhinitis and asthma in certain individuals. ... Hyper IgE syndrome is a heterogeneous group of disorders characterized by recurrent staphylococcal infections, unusual eczema-like skin rashes, severe lung infections that result in pneumatoceles (balloon-like lesions that may be filled with air or pus or scar tissue) and very high concentrations of serum IgE. Some patients have...

IgE, that can specifically recognise an "allergen" (typically this is a protein, such as dust mite DerP1, cat FelD1, grass or ragweed pollen, etc.) has a unique long-lived interaction with its high affinity receptor, Fc epsilon RI, so that basophils and mast cells, capable of mediating inflammatory reactions, become "primed", ready to release chemicals like histamine, leucotrienes and certain interleukins, which cause many of the symptoms we associate with allergy, such as airway constriction in asthma, local inflammation in eczema, increased mucus secretion in allergic rhinitis and increased vascular permeability, ostensibly 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. Although the mechanisms of each response are fairly well understood, why some allergics develop such drastic sensitivities when others merely get a runny nose is still one of science's hot topics. Regulation of IgE levels through control of B cell differentiation to antibody-secreting plasma cells is thought to involve the "low affinity" receptor, Fc epsilon RII or CD23. CD23 may also allow facilitated antigen presentation, an IgE-dependent mechanism whereby B cells expressing CD23 are able to present allergen to (and stimulate) specific T helper cells, causing the perpetuation of a Th2 response, one of the hallmarks of which is the production of more antibodies. Binomial name Dermatophagoides pteronyssinus The house dust mite (Dermatophagoides pteronyssinus), sometimes abbreviated by allergists to HDM, is a cosmopolitan guest in human habitation. ... Species See text. ... Biochemistry is the study of the chemistry of life, a bridge between biology and chemistry that studies how complex chemical reactions give rise to life. ... This article needs to be cleaned up to conform to a higher standard of quality. ... A mast cell (or mastocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. ... Histamine is a biogenic amine chemical involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... Mucus is a slippery secretion of the lining of various membranes in the body (mucous membranes). ... For the play, see Hay Fever. ... Anaphylaxis is a severe and rapid systemic allergic reaction to a trigger substance, called an allergen. ... Plasma cells are B lymphocytes that secrete immunoglobulins (antibodies). ... CD23 or Fc epsilon RII is the low affinty receptor for IgE, an antibody isotype involved in allergy and (arguably) resistance to parasites and is important in regulation of IgE levels. ... CD23 or Fc epsilon RII is the low affinty receptor for IgE, an antibody isotype involved in allergy and (arguably) resistance to parasites and is important in regulation of IgE levels. ... B cells are lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response). ... CD23 or Fc epsilon RII is the low affinty receptor for IgE, an antibody isotype involved in allergy and (arguably) resistance to parasites and is important in regulation of IgE levels. ... T cells are a subset of lymphocytes that play a large role in the immune response. ...

Pharmacology

IgE may be an important target in treatments for allergy and asthma.

Currently, severe allergy and asthma is usually treated with drugs (like anti-histamines) that damp down the late stages of inflammation and relax airway smooth muscle. Unfortunately, these treatments are fairly broad in their action, and so many have unpleasant side effects, and they so may also inhibit important protective responses.

Recently, researchers at The Randall Division of Cell and Molecular Biophysics determined the structure of IgE (3). 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 Fc epsilon RI will enable development of a new generation of allergy drugs that seek to interfere with the IgE-receptor interaction. A new treatment, omalizumab, a monoclonal antibody, recognises IgE not bound to its receptor and is used to neutralise or mop-up existing IgE and prevent it from binding to cells. It may be possible to design treatments cheaper than monoclonal antibodies (for instance, small molecule drugs) that use a similar approach to inhibit IgE binding to its receptor. The Randall Division of Cell and Molecular Biophysics is part of Kings College London and one of Britains finest research institutions - a centre of excellence for study into allergy and asthma; muscle signalling and development; structural biology; muscle biophysics; cell motility and cytoskeleton, and cell imaging. ... Omalizumab (marketed under the name Xolair®) is a drug used mainly in allergy-related asthma therapy, with the purpose of reducing allergic hypersensitivity. ... Monoclonal antibodies (mAb) are antibodies that are identical because they were produced by one type of immune cell, all clones of a single parent cell. ...

In 1975 (Science 189:389-390) Robert N. Hamburger, M.D. published "Peptide Inhibition of the P-K Reaction" based on blocking up to 89% of the IgE receptors on mast cells by the pentapeptide representing amino acids 320 to 324 on the epsilon chain of IgE.

Allergy misconceptions

Naturally, there is far more to allergy than just IgE - many allergic reactions are independent of IgE (e.g. delayed-type hypersensitivity). Our incomplete understanding in many areas of allergy pathogenesis has opened the door for many hypochondriacs and people who operate out of the back of heath food stores to incorrectly put a host of maladies under the umbrella of allergy. The best example of this is food sensitivity. Whilst allergens can indeed be ingested and taken up through the gut (one of the most dangerous hypersensitivities is to peanut allergens), many food sensitivities have no connection to IgE and are mediated by other arms of the immune system. The ELISA food allergy panel can identify specific foods to which a patient has a reaction (either IgE or IgG). Removal of foods causing IgG immune response as measured using the ELISA food panel has been shown to substantially decrease symptoms of Irritable Bowel Syndrome in a several controlled studies. (Gut, 2004) Hypochondria (sometimes hypochondriasis) is the unfounded belief that one is suffering from a serious illness. ... The Enzyme-Linked Immunosorbent Assay (ELISA or EIA for short) is a biochemical technique used in immunology to detect the presence of an antibody or an antigen in a sample. ...

References

1. Annual Review of Immunology 2003 Apr 21;579-628.
2. Journal of Immunology 2005 Apr 15;174(8):5024-32.
3. Nature Immunology 2002 Jul;3(7):681-6.
4. European Journal of Immunology 2003 Apr;33(4):1030-40.
5. Science 1975 August, 189: 389-390
6. Gut 2004; 53(10):1459-64. (Atkinson W, Sheldon TA, Shaath N, Whorwell PJ "Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial" PMID 15361495 Full text}}