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At a glance

A chronic malabsorptive disease of the small intestine resulting from an immune response to ingestion of gluten.

Synonyms

Celiac Sprue; Sprue; Gluten-Sensitive Enteropathy; Gluten Intolerance; Herter Disease; Herter-Heubner Disease; Gee-Herter Disease.

Incidence

For symptomatic gluten-sensitive enteropathy, the incidence is 1:150-1,000 in Europe, but a greater proportion of individuals (1:200-400) may have clinically silent disease. It is estimated to affect about 1% of the population in the United States. The incidence appears to be much lower in the Afro-American and Asian population, which is explained by a lower frequency of human leukocyte antigens (HLA)-DQ2 and HLA-DQ8. Having a second-degree or first-degree relative affected with the disease increases the prevalence to 1:39 and 1:22, respectively.

Genetic inheritance

Multifactorial. The causative genetic component involves an assortment of major histocompatibility complex genes interacting with environmental factors. Celiac disease (CD) is the first HLA-associated disease for which the “at-risk genotypes” have been delineated. In the vast majority (>93%) of patients with CD, genetic susceptibility has been associated with the HLA-DQ2 heterodimer, encoded by the DQA1*0501 and DQB1*02 genes. The remaining minority not expressing DQ2 is positive for DR4 and shows the DQ8 heterodimer, which is encoded by DQA1*0301/DQB1*0302 genes. The two heterodimers DQ2 and DQ8 are located on the surface of antigen-presenting cells and are involved in the binding of peptides to be presented to CD4+ T-lymphocytes. This association supports the importance of CD4+ T-lymphocytes in the pathogenesis of CD, as a T-cell-mediated inflammatory response in the proximal small bowel is made responsible for the intestinal problems. At least 39 non-HLA genes that convene a predisposition to CD have been identified.

Pathophysiology

The mucosal lesions represent an immunologically mediated injury triggered by gluten. The amino-acid residue of gliadin triggers the abnormal immune response. Gluten is found in wheat, rye, barley, triticale, but not oats. The alcohol-soluble prolamine fraction is the component of gluten that is responsible for the symptoms of CD. Depending on the cereal, this prolamine fraction has different names: gliadin in wheat, secalin in rye, hordein in barley, and avenin in oats and in maize it is called zein (however, these latter two [avenin and zein] are non-immunogenic, ie, tolerated by CD patients). Tissue transglutaminase, the major target of autoantibodies in CD, converts glutamine residues of gluten to glutamic acid when it reaches the intestinal lamina propria, thereby enhancing the immunogenicity by significantly increasing DQ binding and T-cell recognition. These gliadin fragments are bound by HLA-DQ2 or HLA-DQ8 on antigen-presenting cells, which in turn activate CD4+ T-cells. Many experts now agree that environmental factors and the composition and function of gut microbiota most likely play a role in the pathogenesis of CD, although their roles remain to be elucidated.

Diagnosis

The favored combination of serologic ...

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