Celiac disease in an autoimmune process in which the body makes antigens and antibodies in the presence of gliadin, the alcohol-soluble fraction of gluten. When gluten is consumed, the body mistakes its own gi tract cells for invader cells and antigens signal the immune system. Antibodies then attack the lining of the small intestine, most specifically the villi, which are the small finger like projections located on the surface of the lining. Overtime this attack on the digestive tract can lead to decreased absorption of nutrients, diarrhea, gi upset, and other less common symptoms such as anemia.
Among the environmental factors, gluten is the most common contributor in the development of Celiac disease. Gluten is present in grains like wheat, rye, oat, and barely and is rich in amino acids proline and glutamine. These residues are resistant to degradation by small intestinal proteases. Therefore, gluten protein is not digested completely and partial digestion leads to creation of multiple peptides. These peptides are generated by the action of enzyme tissue transglutaminase (tTG) which causes deamidation of gluten. The peptides are then presented by HLA DQ2 and HLA DQ8 molecules to T-cells. Both gluten as well as autoantigen tTG induce autoimmune response. In CD patients, gluten consumption leads to the production of tTG antibodies by B cells in small intestinal mucosa that can be detected in the serum. In addition, gluten fragments can cause enterocytes to produce zonulin that loosens the tight junction, leading to intestinal permeability, a characteristic of CD.
Timing of introduction of gluten containing food as a risk factor of CD has been investigated. A study showed that 3 months old infants have a higher risk of developing CD associated auto-antibodies when exposed to gluten in comparison to 4- 6 months old babies exposed to gluten. However, other studies show contradictory results.
Celiac disease has a genetic component, those with a family history of Celiac are at higher risk. The main predisposing genetic factor contributing to Celiac disease is the class II major histocompatibility complex comprising human leukocyte antigen (HLA).
Majority of patients with Celiac are positive for HLA-DQ2 type antigens while a minor fraction of patients are positive for HLA-DQ8. HLA-DQ molecules are present on the surface of antigen presenting cells and act as receptors of processed antigens. The DQ8 and DQ2 molecules present gluten peptides to T-cells in the small intestine. HLA DQ2- restricted gluten specific CD4+ T cells in small intestine induce a pro-inflammatory response, leading to the architectural changes typically observed in the small intestine of CD patients. These T cells are specifically present in CD patients. Non- HLA genes have been also implicated in the pathogenesis of CD. Genome-wide association studies (GWAS) have identified 39 non-HLA celiac disease risk loci. Many of these genes are associated with adaptive and innate immune functions.
Other factors that predispose an individual to CD include pathogens such as Campylobacter jejuni, Adenovirus, and Hepatitis C virus. Resident intestinal microbiota may also play a significant role in CD. It has been shown that celiac patients have altered gut microbial composition compared to non-celiac controls. Future therapy targeted at normalizing the gut microbial composition may prove beneficial for CD.