The Role of Celiac Transglutaminase in Celiac Disease

Celiac disease is a chronic autoimmune disorder triggered by the consumption of gluten-containing grains such as wheat, barley, and rye in genetically susceptible individuals. It affects approximately 1% of the global population, and its prevalence is rising. Gluten, a complex protein, largely contributes to the pathology of celiac disease. However, the exact mechanism by which gluten triggers an autoimmune response has been a topic of extensive research.

One key player in the pathogenesis of celiac disease is celiac transglutaminase, also known as tissue transglutaminase (tTG). It is an enzyme primarily responsible for modifying proteins by creating covalent bonds between glutamine and lysine residues. In individuals with celiac disease, tTG plays a crucial role in the progression of the disease.

When gluten is ingested by someone with celiac disease, it triggers an abnormal immune response leading to inflammation and damage to the small intestine. It is believed that tTG has a critical role in this immune response. The primary mechanism by which tTG contributes to celiac disease is through its interaction with gluten.

Gluten contains specific amino acid sequences that resemble those found in the body’s own proteins, particularly in the gut. This molecular mimicry can lead to the activation of immune cells that recognize these sequences, setting off an inflammatory response. tTG plays a crucial role in this process by modifying the gluten peptides, making them more immunogenic.

Once the gluten peptides are modified, they become recognizable by immune cells, specifically T cells, which are central and orchestrating components of the immune system. These T cells recognize the modified gluten peptides in association with human leukocyte antigen (HLA) molecules on antigen-presenting cells, initiating an immune response.

tTG also contributes to the pathogenesis of celiac disease by promoting intestinal epithelial barrier dysfunction. In a healthy intestine, the epithelial layer acts as a barrier, preventing the entry of harmful substances into the bloodstream. In celiac disease, tTG disrupts the integrity of the intestinal epithelial layer, allowing gluten peptides to penetrate through, leading to an exaggerated immune response.

Furthermore, tTG itself becomes a target of the autoimmune response. Antibodies against tTG, known as anti-tTG antibodies, are present in individuals with celiac disease. These antibodies contribute to the damage of the small intestine by directly targeting tTG, further impairing its enzymatic activity and perpetuating the inflammatory response.

Understanding the role of tTG in celiac disease has led to the development of diagnostic tests for the disease. Measuring anti-tTG antibodies in the blood has become a standard diagnostic tool, as elevated levels of these antibodies are highly specific to celiac disease. Additionally, efforts have been made to develop inhibitors of tTG as potential therapeutic interventions for celiac disease. Inhibiting tTG activity could potentially prevent the modification of gluten peptides, limiting their immunogenicity and reducing the immune response.

In conclusion, celiac transglutaminase plays a crucial role in the pathogenesis of celiac disease. Its ability to modify gluten peptides, promote intestinal barrier dysfunction, and become a target of the autoimmune response all contribute to the development and progression of the disease. Understanding the role of tTG has not only provided insights into the pathophysiology of celiac disease but has also opened doors for diagnostic and therapeutic advancements in the field.