What is Celiac Disease?
Celiac disease is an autoimmune disorder in response to the digestion of gluten
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What is Celiac Disease?
Celiac disease is an autoimmune disorder in response to the digestion of gluten. Gluten is a protein found in wheat, barley, rye and other grains and is commonly included in many processed and packaged foods. When an affected individual consumes a gluten-containing product, their immune system reacts aberrantly and damages the lining of their small intestine. This severe damage to the villi of the intestine prevents the absorption of vitamins, minerals and nutrients and leads to serious problems.
What Causes Celiac Disease?
The serious damage to the intestinal lining is due to the presence of gluten and an aberrant immune response. Celiac disease is strongly associated with specific types or alleles of HLA-DQA1 and HLA-DQB1, important components of the immune system. These alleles are HLA-DQA1*05, HLA-DQB1*02 and HLA-DQB1*0302. After affected individuals consume gluten, a heterodimer of the DQA1 and DQB1 subunits forms, and this is recognized by the T cell receptors in the intestinal mucosa and an immune response is initiated. The inflammation from this immune response leads to severe damage of the intestinal lining.
Genetics of Celiac Disease
HLA-DQA1*05, HLA-DQB1*02 and HLA-DQB1*0302 are the human leukocyte antigen (HLA) alleles associated with celiac disease. The HLA complex is an important part of the immune system, helping to distinguish between the body’s own proteins and foreign proteins. In celiac-affected individuals, the mutated HLA-DQA1 and HLA-DQB1 components form a complex to display the gliadin fraction of the gluten protein to the immune system, initiating an immune response.
Individuals that have one or more of the celiac-associated alleles (HLA-DQA1*05, HLA-DQB1*02, HLA-DQB1*0302) have increased risk of developing celiac disease. However, this is not a diagnostic test, as only a subset of people with these alleles will develop celiac disease. If these alleles are absent, the diagnosis of celiac disease can essentially be excluded, as there is a less than 0.04% chance of developing celiac disease in people that don’t have one or more of these at-risk alleles.
What Other Factors Contribute to Celiac Disease?
Almost all celiac-affected people carry one or more of the increased risk HLA alleles (DQA1*05, DQB1*02, DQB1*0302). However, there are many people who carry these alleles who never develop celiac disease. This indicates that other genetic or environmental factors are also involved in the development of celiac disease. Several other possible susceptibility genes are currently being investigated but further research on these genes is still required. Traumatic events may be a trigger in the development of celiac disease. These could include surgery, pregnancy, childbirth, viral infections or severe emotional stress. Other diseases may also increase the risk of developing celiac disease. These health problems include other autoimmune disorders (e.g. diabetes, rheumatoid arthritis, lupus), Down syndrome, thyroid problems and intestinal cancer.
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Recommended Links: Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PH, Hadjivassiliou M, Kaukinen K, Kelly CP, Leonard JN, Lundin KE, Murray JA, Sanders DS,Walker MM, Zingone F, Ciacci C (2013). The Oslo definitions for coeliac disease and related terms. Gut 62(1): 43-52.
Rubio-Tapia A, Ludvigsson JF, Brantner TL, Murray JA, Everhart JE (2012). The prevalence of celiac disease in the United States. American Journal of Gastroenterology. 107(10): 1538-44.