Celiac Disease Pathogenesis

Celiac disease is an autoimmune condition where the body responds to gluten in the diet by the immune system going in an overdrive and affecting the inner walls of the small intestines.

Pathogenesis of celiac disease

Celiac disease results from activation of both a cell-mediated (T-cell) and humoral (B-cell) immune response. This activation results from exposure to the glutens. Glutens are basically prolamines and glutenins or proteins present in wheat, barley, rye, and (rarely) oats.

The sensitivity to gluten is further determined by genetics. There is a high level of concordance among monozygotic twins to the tune of 70% supporting the genetic association theory.

There is an association with certain type II human leukocyte antigens (HLA). HLA-DQ2 is found in up to 95% of patients with celiac disease. The remaining patients mainly have HLA-DQ8. The expression of these HLA-DQ2 or HLA-DQ8 molecules is necessary, but not sufficient, for the disease to develop.

These are thus not the only genes responsible for risk for celiac disease. HLA genes are estimated to contribute to about one-third of the genetic variance of the disease.

It is found that among the general population the risk of celiac disease is 1% while presence of DQ2 or DQ8+ states makes it 2 to 3%. Among first degree relatives with unknown HLA type the risk if 10 to 15% while among first-degree relatives with DQ2 or DQ8+ states the risk is 20 to 30%.

There is in addition presence of autoantibodies to the connective-tissue element surrounding smooth muscle known as endomysium. The presence of these autoantibodies is specific for celiac disease.

The target of these autoantibodies is enzyme tissue transglutaminase (tTG). This enzyme plays an important role in pathogenesis of celiac disease. It works by deamidating gliadin which results in greater proliferative response of gliadin-specific T-cells that lead to mucosal inflammation and further B-cell activation in patients with HLA-DQ2 or -DQ8.

Risks associated with celiac disease

There is an increased risk of celiac disease associated with certain autoimmune and other conditions. Some of these include:-

  • First-degree and second-degree relatives of a sufferer. The risk is 5–15% in general among first degree relatives of a patient and is 10 to 30% if the individual is DQ2 or DQ8 positive.
  • Down’s syndrome – the risk of getting celiac disease is 12%
  • Chronic active hepatitis
  • Type 1 diabetes mellitus raises risk of celiac disease by 5 to 5%
  • Autoimmune thyroid disease raises risk of celiac disease by 5%
  • Lymphocytic colitis raises risk of celiac disease by 15 to 27%
  • Irritable bowel syndrome
  • Chronic fatigue syndrome raises risk of celiac disease by 2%

Celiac disease in itself if left untreated leads to an increased risk of:-

  • 1.3:1 ratio of increase in risk of cancers
  • Small bowel cancers
  • Oropharyngeal cancers and tumors
  • Unexplained infertility seen in 12% patients
  • Osteoporosis with long term sufferers

Further Reading

Last Updated: Jan 23, 2023

Dr. Ananya Mandal

Written by

Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.

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