Immunoglobulin E—an Innocent Bystander in Host Defense?

Excerpt

Discoveries of physiology often precede anatomy in immunology research. Forty-five years before the discovery of IgE, Prausnitz and Küstner found that allergy can be transferred by sera from allergic patients in 1921 [1]. Tested by erythema-wheal assays, this serum fraction was named “reagin.” With the advances in electrophoresis and ultracentrifugation between the 1930s and 1960s, IgG, IgM, IgA, and IgD were sequentially discovered. By the end of 1964, most immunologists and allergists believed that reagin is an allergen-specific IgA antibody. Eventually, in 1966, Ishizaka et al. discovered the immunoglobulin responsible for allergy—IgE, named after the erythema-wheal. IgE was the last immunoglobulin discovered due to its over 1000 times lower blood concentration in healthy controls compared with the other immunoglobulin classes. Although scarce, IgE characteristically has rapid, potent, and broad effects through FcεRI and CD23 on a wide range of cell types [2]. The evolutionary persistence of IgE suggests an important role in host defense [2]. IgE was shown to opsonize Schistosoma mansoni for killing by eosinophils, to induce strong responses of skin mast cells and basophils to arthropods bites, and to activate mast cells to release proteases that neutralize venoms [2]. In sharp contrast to the abundant studies on increased IgE levels in the context of allergy, the clinical implication of decreased IgE levels remain largely neglected. In this issue, Lawrence et al. report a frequent lack of IgE in addition to other immunoglobulins in the majority of common variable immunodeficiency (CVID) patients. This should ignite new research into host defense functions of IgE [3]. …