Fig. 14.5 Netherton’s syndrome illustrates the association of proteases with the development of high levels of IgE and allergy. This 26-year-old man with Netherton’s syndrome, caused by a deficiency in the protease inhibitor SPINK5, had persistent erythroderma (redness of the skin), recurrent infections of the skin and other tissues, and multiple food allergies associated with high serum IgE levels. In the top photograph, large erythematous plaques covered with scales and erosions are visible over the upper trunk. The lower panel shows a section through the skin of the same patient. Note the psoriasis-like hyperplasia of the epidermis. Neutrophils are also present in the epidermis. In the dermis, a perivascular infiltrate is evident. Although not discernible at this magnification, the infiltrate contains both mononuclear cells and neutrophils. Source: Sprecher, E., et al.: Clin. Exp. Dermatol. 2004, 29:513–517.
cause allergic reactions in workers preparing the enzyme. Allergies caused by environmental allergens present in the workplace are called occupational allergies. Although Der p 1 and papain are potent allergens, not all allergens are enzymes. In fact, two allergens identified from filarial worms are enzyme inhibitors, and, in general, most allergenic pollen-derived proteins do not seem to possess enzymatic activity.
Knowledge of the identity of allergenic proteins can be important to public health and can have economic significance, as illustrated by the following cautionary tale. Some years ago, the gene for 2S albumin from Brazil nuts, a protein that is rich in methionine and cysteine, was transferred by genetic engineering into soybeans intended for animal feed. This was done to improve the nutritional value of soybeans, which are intrinsically poor in these sulfur-containing amino acids. This experiment led to the discovery that 2S albumin is the major Brazil nut allergen. Injection of extracts of the genetically modified soybeans into the epidermis triggered an allergic skin response in people allergic to Brazil nuts. As there could be no guarantee that the modified soybeans could be kept out of the human food chain if they were produced on a large scale, development of this genetically modified food was abandoned.
14-3 Genetic factors contribute to the development of IgE-mediated allergic disease.
Susceptibility to development of allergic disease has both genetic and environmental components. In studies performed in Western industrialized countries, up to 40% of the test population shows an exaggerated tendency to mount IgE responses to a wide variety of common environmental allergens. Atopic individuals often develop two or more allergic diseases such as allergic rhinoconjunctivitis, allergic asthma, or allergic eczema. Individuals who manifest all three of these disorders are said to express the atopic triad.