For the antibody, see Immunoglobulin E (IgE). IGE is also an abbreviation for the "Eidgenössisches Institut für Geistiges Eigentum", the Swiss Federal Institute of Intellectual Property.

IGE (Internet Gaming Entertainment) is one of the largest MMORPG services companies, with offices in Los Angeles, Miami, and China. IGE is one of the main players in virtual economy services, also known in the MMORPG industry as secondary market. Members of the gaming community are often critical of IGE, as its services may allow players to break the rules of online games.

The co-founders of IGE are Brock Pierce, a former child movie star , and Alan Debonneville. Pierce was also the co-founder of the controversial failed dot-com Digital Entertainment Network (DEN). Media reports claim that Marc Collins-Rector is a silent partner in IGE. IGE initially used an address in the city of Marbella, Spain, where Collins-Rector, Shackely, and Pierce shared a villa until it was raided by Interpol in 2002

In January 2004, IGE acquired its major competitor, Yantis Enterprises, run by another controversial secondary market figure, Jonathan Yantis for an undisclosed sum. IGE's parent company, RPG Holdings purchased Allakhazam.com in November 2005 and was announced in May 2006. Allakhazam is a popular MMORPG community site for a wide variety of games that IGE's services cater for; however, the site continues to pride itself on not supporting the trade of virtual currencies in the real economy, typically breaking and/or removing any links to sites (including IGE) that perform such trades. This marks the further expansion of this company's presence in online gaming communities. This purchase followed that of ThottBot.com.

While many users left because of the purchase, the site is still extremely popular with players of many major MMOs.

Affinity Media was the parent company of IGE, though the company no longer has any ownership stake. Affinity Media's senior vice president of business development John Maffei, noted that "we’re no longer in that business." Affinity retains control of Allakhazam.com, Thottbot.com, and has since purchased Wowhead.com

Like all the other in-game currency sellers, IGE's vast majority of the revenue comes from selling the World of Warcraft gold. Its website traffic, and allegedly its revenue has been declining since 2006 for the increased competition from the in-game currency sellers based in China, and the constant bombardment of anti-real-money trading measures by Blizzard Entertainment, the publisher of World of Warcraft.

Games available

• Anarchy Online
• Auto Assault
• City of Heroes
• Dark Age of Camelot
• Dungeons & Dragons Online
• Eve Online
• Everquest
• Everquest II
• Final Fantasy XI
• Guild Wars
• Lineage II
• Lord of the Rings Online
• RF Online
• Star Wars Galaxies
• Vanguard: Saga of Heroes
• World of Warcraft

References

External links

• Main IGE website
• Allakhazam.com website
• Thottbot.com website
• "The Truth About IGE", an article about IGE and it's founder's supposed background(s)
• The Rise and Fall of IGE
• Another one of IGE's site sold.
• WOW4CHEAP - Purchased by IGE in 2007.

Although IgE is typically the least abundant isotype - blood serum IgE levels in a normal ("non-atopic") individual are ~75 ng/ml, compared to 10 mg/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.

IgE was discovered in 1966 by the Japanese scientist Kimishige Ishizaka.

Receptors

• FcεRI, the high-affinity IgE receptor
• FcεRII, also known as CD23, is the low-affinity IgE receptor

IgE can upregulate the expression of both Fcε receptors. FcεRI is expressed only on mast cells and/or basophils in both mice and humans. Aggregation of its antigens and binding of IgE to the FcεRI on mast cells causes degranulation and the release of mediators from the cells, while basophils cross-linked with IgE release type 2 cytokines like interleukin-4 (IL-4) and interleukin-13 (IL-13) and other inflammatory mediators. The low affinity receptor (FcεRII) is always expressed on B cells, but its expression can be induced on the surfaces of macrophages, eosinophils, platelets and some T cells by IL-4. This receptor is implicated in pathogenicity during malaria.

Physiology

Although it is not yet well understood, IgE may play an important role in the immune system’s recognition of cancer, 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 undesirable side effects.

Role in disease

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, FcεRI, so that basophils and mast cells, capable of mediating inflammatory reactions, become "primed", ready to release chemicals like histamine, leukotrienes 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, FcεRII 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.

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; they may also inhibit important protective responses.

In 2002, researchers at The Randall Division of Cell and Molecular Biophysics determined the structure of IgE. 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. 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.

In 1975 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.

See also

• Antibodies
• IgM, IgA, IgD, IgG
• Phadia

References