Coeliac Disease

[irish daveyboy]

Alessio Fasano, M.D.

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Celiac disease is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains (including wheat, rye, and barley) in genetically susceptible persons.

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The disease is associated with HLA-DQ2 in 90 to 95 percent of cases and with HLA-DQ8 in 5 to 10 percent of cases and is self-perpetuating in the continued presence of gluten.

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It is the interplay between genes (both HLA and other types) and environment (i.e., gluten) that leads to the intestinal damage that is typical of the disease.Under physiologic circumstances, this interplay is prevented by competent intercellular tight junctions, structures that limit the passage of macromolecules (including gluten peptides) across the intestinal epithelial barrier.

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Recent evidence suggests that the gluten-induced up-regulation of zonulin, an intestinal peptide involved in the regulation of tight junctions, is responsible, at least in part, for the aberrant increase in gut permeability that is characteristic of the early phase of celiac disease and the subsequent abnormal passage of gluten into the lamina propria.

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The protein is deamidated by tissue transglutaminase in the lamina propria and is then recognized by antigen-presenting cells bearing HLA-DQ2 or DQ8, thereby triggering the autoimmune reaction of celiac disease.

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Given the undisputable role of gluten in causing inflammation and immune-mediated tissue damage, celiac disease represents a unique model of autoimmunity in which, in contrast to all other autoimmune diseases, a close genetic association with HLA-DQ2, DQ8, or both; a highly specific humoral autoimmune response (autoantibodies against tissue transglutaminase); and most important, the triggering environmental factor (gluten) have all been identified.

This information provides the rationale for the treatment of the disease based on complete avoidance of gluten-containing grains, a task complicated by the lack of a clear food-labelling policy.

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Epidemiologic studies conducted during the past decade, using specific and sensitive serologic tests, have revealed that coeliac disease is one of the most common lifelong disorders in both Europe and the United States.

The clinical presentation of this condition can range from the typical syndrome of malabsorption (chronic diarrhoea, weight loss, and abdominal distension) to symptoms and conditions that can affect any organ system.

Since the onset of celiac disease may be atypical or even silent, many cases remain undiagnosed and thus carry a risk of long-term complications, including osteoporosis, infertility, and cancer.

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In this issue of the Journal, the article by M

[lizard00]

The prevalence of the disease and the burden of illness related to this condition, particularly if it is not treated, are so high as to potentially support a policy of screening of the general population.

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Celiac disease satisfies the five criteria of the World Health Organization for justifying general screening.

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First, early clinical detection of the disease could be difficult, as suggested by M