40 years with IgE



Discovery and History of IgE

S.G.O. Johansson

Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institute and Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden

The presence in blood of a factor mediating allergy was first observed in 1919 by Ramirez (1). However, it was not until 1967 that a new immunoglobulin class carrying the classical reaginic activity became known. Based on data on the unique physico-chemical structure of IgND and the unique antigenic determinants of IgND (2) and γE (3) the WHO Immunoglobulin Reference Centre in Lausanne in February 1968 officially announced the fifth, and last, class of immunoglobulins, IgE (4).

Knowledge about IgE and access to IgE has had a significant impact on our understanding of allergy. The immunological mechanisms behind the allergic inflammation responsible for the symptoms of allergy in different organs can now be analyzed and characterized as a part of the clinical diagnosis and follow-up. Classical serological approaches can be applied and detection and quantitation of the responsible IgE antibody is now an important routine for diagnosis, monitoring and judgment of the prognosis of disease as well as therapy evaluation.

Using IgE antibodies the quality of allergen preparations used for skin testing, allergen provocation and allergen specific immunotherapy (ASIT), has been improved. It has been shown that an allergen extract of a homogenous source, e.g. peanut, actually contains many, non-cross reacting proteins, often referred to as components. The clinical importance of an IgE-sensitization to e.g. peanut is dependent on the components involved and can vary from very mild or no symptoms to a risk for anaphylaxis.

ASIT was introduced 100 years ago based on an incorrect understanding. ASIT does not prevent an immunologic sensitization, like vaccination with viral antigens, but neutralizes the IgE antibody in vivo probably by stimulating protective immune reactions. Today ASIT can be used with immuno potent but non-allergenic preparations of recombinant allergens, be given sublingually or directly into lymph nodes and more interesting developments are under testing.

Since a few years it is possible to reduce circulating IgE, and thus down-regulate the number of IgE-receptors on the basophils and mast cells, by injection of a humanized monoclonal anti-IgE, omalizumab. This approach will reduce or even eliminate any IgE-mediated allergy disregarding what allergenic component is causing the symptoms. This treatment is today officially available only for severe, persistent allergic asthma but clinical experience is building up on the selection of treatment responders and therapy monitoring also in other IgE-mediated diseases.

Access to IgE has provided the possibility to increase our understanding of the inflammation behind allergy, to identify and evaluate the IgE-sensitization mediating the disease, to diagnose and follow-up allergic patients, to characterize and standardize allergen preparations and to be the basis for immuno-modulating treatments. Better understanding has helped us communicate with colleagues, patients, authorities and the press. These improvements are important since we have to tackle the problems of an increasing prevalence of allergy.

References

1. Ramirez MA: Horse asthma following blood transfusion: Report on a case. JAMA 1919;73:984.

2. Johansson SGO, Bennich H. Studies on a new class of human immunoglobulins. I. Immunological properties. In: Killander J, ed. Gammaglobulins. Structure and control of biosynthesis. Stockholm: Almqvist & Wiksell, 1967:193-197.

3. Ishizaka K, Ishizaka T: Identification of (E-antibodies as a carrier of reaginic activity. J Immunol 1967,99:1187.

4. Bennich HH, Ishizaka K, Johansson SGO, et al.: Immunoglobulin E, a new class of human immunoglobulin. Bull World Health Organ 1968,38:151–152.

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