Genetic variation in the beta subunit of the high affinity IgE receptor and atopy and asthma.
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Biomedical subjects
Publications and source records attributed to William Cookson.
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Asthma and eczema (atopic dermatitis) are the most common chronic diseases of childhood. These diseases are characterized by the production of high levels of immunoglobulin E in response to common allergens. Their development depends on both genetic and environmental factors. Over the past few years, several genes and genetic loci that are associated with increased susceptibility to asthma and atopic dermatitis have been described. Many of these genes are expressed in the mucosa and epidermis, indicating that events at epithelial-cell surfaces might be driving disease processes. This review describes the mechanisms of innate epithelial immunity and the role of microbial factors in providing protection from disease development. Understanding events at the epithelial-cell surface might provide new insights for the development of new treatments for inflammatory epithelial disease.
Recently, a novel gene was reported to underlie asthma. Linkage to the short arm of chromosome 20 in a genome screen was followed by positive tests of association that centre on the gene for a membrane-anchored zinc-dependent metalloproteinase known as ADAM33. The domain structure of the ADAM33 protein gives capabilities of proteolysis, adhesion, cell fusion and intracellular signalling. Although its function is at present unknown, these potential actions of ADAM33 provide many possibilities for further research.
Asthma and eczema (atopic dermatitis) are characterized by a number of unexplained phenomena: the familial aggregation of disease, the initiation of disease by apparently trivial exposure to allergens, the preferential transmission of disease from affected mothers and the large increase in prevalence of disease in Westernized societies in the last century. A number of genes and chromosomal regions have been identified that consistently show linkage to asthma and its related phenotypes. Known loci modify the strength of the atopic response, nonspecific inflammation, the ability to respond to particular allergens and nonspecific airway reactivity. Eczema has been shown to be due to a different set of genetic loci that are shared with other skin diseases such as psoriasis and leprosy. Genetic and genomic studies both provide evidence that epithelial surfaces are active in the induction of allergic disease.
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