From the Guidelines
Celiac disease is an immunological disorder induced by gluten ingestion in individuals with genetic susceptibility, characterized by villous atrophy, intra-epithelial lymphocytosis, and crypt hyperplasia of the small bowel. The disease primarily affects the small bowel, but its clinical manifestations are broad, comprising both intestinal and extra-intestinal symptoms 1. The etiology of celiac disease involves the ingestion of gluten, a storage protein of the cereal grains wheat, rye, and barley, which triggers an autoimmune reaction involving type 2 transglutaminase (TG2) in genetically susceptible individuals 1.
Key Factors in Celiac Disease Etiology
- Genetic susceptibility, particularly the presence of HLA-DQ2 or HLA-DQ8 molecules, is a crucial factor, with nearly 100% of individuals diagnosed with celiac disease exhibiting this specific genetic profile 1.
- Gluten exposure is the primary environmental trigger, with the protein being incompletely digested by gastric, pancreatic, and brush border peptidases, leaving large peptides that trigger the autoimmune reaction 1.
- The autoimmune reaction involves the formation of anti-type 2 transglutaminase antibodies (TG2Ab), pro-inflammatory cytokines, lymphocyte infiltration, and subsequent tissue injury, leading to crypt hyperplasia and villous atrophy 1.
Diagnosis and Genetic Correlation
The diagnosis of celiac disease in adulthood is based on serology (TG2Ab) and duodenal biopsy while the patient is on a gluten-containing diet, with HLA typing playing a crucial role in ruling out the condition when the results are negative 1. The presence of TG2Ab in the serum and duodenal histological alterations usually makes the diagnosis straightforward, supported by guidelines from various scientific societies 1.
Conclusion is not allowed, so the answer just ends here.
From the Research
Celiac Disease Etiology
- Celiac disease is an immune-mediated, multisystem disorder that affects genetically susceptible individuals who are exposed to gluten-containing grains such as wheat, barley, and rye 2.
- The disease is characterized by the presence of circulating auto-antibodies, an enteropathy, and extra-intestinal manifestations triggered by exposure to the gliadin fraction of gluten 3.
- The immune response in celiac disease involves the adaptive and innate immune systems, and is characterized by the presence of anti-gluten and anti-transglutaminase 2 antibodies, lymphocytic infiltration, and expression of multiple cytokines and other signaling proteins 4.
- Celiac disease is caused by an immune-mediated reaction to ingested gluten in genetically susceptible persons 5.
Genetic Susceptibility
- Celiac disease develops in genetically predisposed individuals, with certain human leukocyte antigen alleles (DQ2 or DQ8) increasing the risk of developing the disease 2, 3.
- Genetic testing for these alleles may be performed in select cases to help diagnose celiac disease 2.
Gluten Exposure
- Exposure to gluten is the primary trigger for celiac disease, and the only effective treatment is a strict gluten-free diet for life 6, 2, 4, 5.
- Even in asymptomatic patients, eliminating gluten can bring about health benefits, particularly in relation to bone health and a decrease in the incidence of small bowel malignancy 3.