From IgE to Anti‐IgE: Where do we stand?

From IgE to Anti-IgE: Where do we stand?Allergy and IgE -a pair of shoes.The term ''allergy'' was originally introduced by von Pirquet in 1906 meaning ''changed reactivity'' of a host after the second or subsequent contact with an ''agent''.The clinical features of this hypersensitivity reaction comprise asthma, hay fever, urticaria and eczema, and were originally termed ''atopy'' by Coca and Cooke in 1923.The first implication of a transferable/soluble factor as the mediator of an allergic reaction was published in 1919.In this case report, Ramirez describes a man who experienced an acute asthmatic episode while entering a horse-drawn coach in New York's Central Park two weeks after having received a 600-ml blood transfusion from a man with a known horse allergy (1).The first scientific description of the mechanism of the allergic reaction was provided in 1921 by Prausnitz and Ku¨ster, who showed that a serum factor (''reagin'') was able to passively transfer hypersensitivity reactions from an allergic to the skin of a non-allergic patient (2).But only after another forty-five years could Ishizaka and colleagues (3, 4) and Johannson and colleagues (5) independently show that this ''reagin'' was a novel class of serum antibodies -immunoglobulin-E: IgE (6).Now, another 35 years later, we stand on the brink of a novel therapeutic option for the treatment of allergic diseases, by directly targeting increased serum IgE with antagonizing antibodies: anti-IgE antibodies.The prevalence of asthma, hay fever and other IgEmediated diseases (7) has increased dramatically in industrialized countries over the last decades, making allergies a very serious public health problem (8-10).Asthma prevalence rates increased by 75% in the Unites States between 1980 and 1994 (11).The prevalence of allergic diseases is even higher in children (12), where asthma is the most common chronic illness overall.Twenty-three percent of British children aged 6-7 years, and 21% of British children aged 12-14 years (13) suffer from asthma.Despite better understanding of pathophysiology and improved treatment protocols for allergic diseases, overall morbidity and even mortality rates of asthma have increased in the last two decades (14).The most robust predisposing factor for the development of allergic diseases is atopy, the genetic predisposition to produce allergen-specific IgE (15). I. Role of IgE in allergic diseasesIgE, similar to other immunoglobulins, is comprised of two heavy and two light chains (Fig. 1).It is produced by allergen-specific plasma cells after isotype switch to the epsilon-chain.IgE production is mainly under the control of T cells and T-cell cytokines (Fig. 2) (16, 17).