Pathology

Pathology

Celiac disease is a condition in which there is inflammation of the mucosa of the upper small bowel that improves when gluten is withdrawn from the diet and relapses when gluten is reintroduced.It is Also called Gluten sensitive enteropathy.

Prolamins which are part of gluten,(gliadin from wheat, hordeins from barley, secalins from rye) are damaging factors. These proteins are resistant to digestion by pepsin and chymotrypsin because of their high glutamine and proline content and remain in the intestinal lumen triggering immune responses.

Gluten containing plants taxonomy is as follows

Immunology. Gliadin peptides pass through the epithelium (para- and/or intracellularly) and are deaminated by tissue transglutaminase which increases their immunogenicity. Gliadin peptides then bind to antigen-presenting cells which interact with CD4⁺ T cells in the lamina propria via HLA class II molecules DQ2 or DQ8. These T cells produce pro-inflammatory cytokines, particularly interferon-γ. CD4⁺ T cells also interact with B cells to produce endomysial and tissue transglutaminase antibodies. Gliadin peptides also cause release of interleukin-15 from enterocytes, activating intraepithelial lymphocytes with a natural killer cell marker. This inflammatory cascade releases metalloproteinases and other mediators that contribute to the villous atrophy and crypt hyperplasia which specify the disease.

The mucosa of the proximal small bowel is predominantly affected, the mucosal damage decreasing in severity towards the ileum as gluten is digested into smaller ‘non-toxic’ fragments.

Genetic factors. There is an increased incidence of celiac disease within families 10–15% of 1st-degree relatives will have the condition, although it may be asymptomatic. The concordance rate in identical twins is about 70%.

HLA-DQ2 and HLA-DQ8  are associated with CD. Over 90% of patients will have HLA-DQ2, compared with 20–30% of the general population.HLA genes are responsible for <50% of the genetic cause of the disease. Many unaffected people also have these genes, so other factors must also be involved. Non-HLA genes may also contribute to celiac disease, e.g. chromosome regions 19p13.1, 11q, 5q31-33 and 6q21-22. The CD28/CTLA4/ILO5 gene cluster has also shown linkage with celiac disease.

Environmental factors. Breast-feeding,age of introduction of gluten into the diet and rotavirus infection in infancy also increases the risk, and adenovirus-12 which has sequence homology with α-gliadin has been suspected as a causative agent.