Celiac disease is an autoimmune disorder where the immune system mistakenly attacks the small intestine. This response is triggered by ingesting gluten, a protein in wheat, barley, and rye, which impairs nutrient absorption and causes various symptoms. Unlike a food allergy or intolerance, celiac disease is a complex condition rooted in a specific and harmful immune reaction.
The Autoimmune Response in Celiac Disease
The process begins when gluten is consumed. Gluten is resistant to complete digestion, allowing large protein fragments, or peptides, to remain in the small intestine. These undigested peptides can cross the intestinal lining and enter the underlying tissue.
Once inside the intestinal tissue, an enzyme called tissue transglutaminase (tTG) modifies the gluten peptides through a process called deamidation. This chemical change makes the gluten fragments more likely to provoke an immune response. In genetically predisposed individuals, the immune system incorrectly identifies this modified gluten-tTG complex as a threat.
The identification of the tTG-gluten complex as a threat triggers an inflammatory cascade. Specific immune cells, called CD4+ T-cells, recognize the complex and release chemical messengers known as cytokines. These cytokines signal other immune cells to join the attack, leading to chronic inflammation directed at the lining of the small intestine.
This sustained immune assault damages the small intestine’s villi, which are tiny projections responsible for absorbing nutrients. The inflammation leads to villous atrophy, where the villi become flattened, reducing the surface area available for absorption. This damage is the direct result of the body’s immune system attacking the intestinal tissue.
Genetic and Environmental Triggers
Celiac disease develops from an interaction between genetic factors and an environmental trigger. The primary genetic determinants are variants of the human leukocyte antigen (HLA) genes, specifically HLA-DQ2 and HLA-DQ8. These genes help the immune system distinguish the body’s proteins from those of foreign invaders.
The presence of HLA-DQ2 or HLA-DQ8 is necessary to develop the disease, with about 95% of patients having the HLA-DQ2 variant. These specific HLA proteins bind strongly to the modified gluten peptides, presenting them to the immune system. The absence of both genes makes developing celiac disease extremely unlikely.
These genes are required but not sufficient to cause the disease. About 30% of the population carries at least one of these genes, yet only about 1% develops celiac disease. The primary environmental trigger is ingesting gluten, as the disease will not manifest in a susceptible person without gluten exposure.
Researchers are investigating other potential environmental influences that may contribute to activating the disease. Factors such as the timing of gluten introduction in infancy, gastrointestinal infections, and alterations in the gut microbiome are areas of study. These elements might play a role in modulating the immune system’s response to gluten.
Distinguishing Celiac Disease from Other Gluten Reactions
Celiac disease is distinct from other gluten-related conditions. A wheat allergy is a classic allergic reaction mediated by Immunoglobulin E (IgE) antibodies produced in response to wheat proteins. This response is rapid, with symptoms like hives or breathing difficulties appearing quickly, unlike the delayed autoimmune attack of celiac disease.
Non-celiac gluten sensitivity (NCGS) causes symptoms similar to celiac disease, such as bloating, pain, and fatigue after consuming gluten. The difference is the absence of the biological markers defining celiac disease. People with NCGS do not produce anti-tTG autoantibodies or experience the associated intestinal damage.
The mechanism behind NCGS is not fully understood. It is not an autoimmune disease, as there is no evidence the immune system attacks the body’s tissues. Diagnosis is made by exclusion after ruling out celiac disease and wheat allergy. While symptoms improve on a gluten-free diet, NCGS does not carry the same risk of long-term complications.
Diagnosis and Associated Conditions
Diagnosing celiac disease is a multi-step process done while the individual consumes gluten. The first step is a blood test to detect autoantibodies, specifically the anti-tissue transglutaminase Immunoglobulin A (tTG-IgA) antibody. These antibodies indicate the immune system is responding to the body’s own tTG enzyme.
If blood tests are positive, the diagnosis is confirmed with an upper endoscopy and biopsy. A gastroenterologist examines the small intestine and takes tissue samples. These samples are analyzed for characteristic damage, including villous atrophy and increased inflammatory cells, which provides proof of the autoimmune attack.
The autoimmune nature of celiac disease is highlighted by its link to other autoimmune conditions. People with celiac disease have a higher risk of developing other disorders where the immune system attacks different parts of the body. The most common associated conditions are Type 1 diabetes and autoimmune thyroid disease. This clustering of diseases is linked to shared genetic predispositions.