How does gluten trigger symptoms in celiac disease?

Understanding How Gluten Triggers Symptoms in Celiac Disease

Celiac disease is an autoimmune disorder that affects millions worldwide, causing a range of symptoms when individuals consume gluten, a protein found in wheat, barley, and rye. The mechanism by which gluten triggers symptoms in celiac disease involves a complex immune response that damages the small intestine.

When a person with celiac disease ingests gluten, the protein is partially digested into smaller fragments called peptides. One of these peptides, known as gliadin, plays a central role in triggering the immune reaction. In the small intestine, gliadin interacts with the enzyme tissue transglutaminase (tTG), which modifies the gliadin peptides. This modification increases their ability to bind to specific immune system molecules called human leukocyte antigen (HLA) DQ2 or DQ8, which are present in genetically predisposed individuals.

The binding of modified gliadin peptides to HLA molecules activates T cells, a type of white blood cell involved in immune defense. These activated T cells mistakenly recognize the gliadin as harmful and initiate an inflammatory response. This inflammation leads to damage of the intestinal lining, specifically the villi—tiny finger-like projections responsible for nutrient absorption. The villous atrophy that results reduces the surface area of the intestine, impairing nutrient absorption and causing symptoms such as diarrhea, abdominal pain, bloating, and malnutrition.

Additionally, the immune response in celiac disease can produce antibodies against tTG and gliadin, which are useful markers for diagnosis. The chronic inflammation and intestinal damage can also lead to complications if untreated, including anemia, osteoporosis, and increased risk of certain cancers.

The only effective treatment for celiac disease is a strict, lifelong gluten-free diet, which allows the intestinal lining to heal and prevents further immune activation. Understanding the immune mechanisms behind gluten-triggered symptoms is crucial for developing better diagnostic tools and potential therapies for this condition.