Celiac disease is a serious autoimmune disorder that affects one out of every 100 people. The immune system is triggered by the presence of gluten, a protein found in cereal grains. Aside from attacking gluten, the immune response also targets the bowel as if the small intestine were a pathogen. If the small intestine is injured by the immune response, it can absorb much less nutrition.
Researchers are still mystified as to the exact means by which gluten triggers the immune system. They have considered both mutations in the HLA-DQ gene related to immunity and a bevy of external factors that include drugs, food, infections, surgery, toxins, and vaccinations. (Related: Gluten intolerance may not exist at all says surprising new study.)
The latest potential cause for celiac disease is food additives. In particular, researchers looked at the bacterial enzyme called microbial transglutaminase, which sees a lot of use in processing food products such as baked goods, dairy products, and meat.
"Microbial transglutaminase can glue together proteins, so it's used to improve food texture, palatability and shelf-life," explained AESKU.KIPP Institute researcher Aaron Lerner. "This enzyme functions like the transglutaminase produced by our body, which is known to be the target of autoimmunity in celiac disease."
Lerner and his colleague Dr. Matthias Torsten found a direct link between the increasing use of enzymes as food additives in baked goods and the growing number of celiac disease cases in the last 40 years. They warned that the microbial transglutaminase used by the food industry is arranged differently than the natural transglutaminase produced by the human body and the bacteria living in the gut.
Furthermore, the amount of transglutaminase produced by the gut bacteria can be affected by external factors. The microbial population could change due to antibiotics, infection, stress, and eating industrially processed foods with microbial transglutaminase. They could end up producing higher levels of enzymes.
Gluten's durability is what made it invaluable in getting baked goods to rise and maintain their shape. But it is difficult to digest by healthy people, much less patients with celiac disease.
"The gluten protein fragments or 'peptides' that remain after digestion are highly susceptible to transglutaminase, which modifies them to make a variety of new peptides," said Lerner. "These unusual peptides are particularly likely to resist further breakdown, and to be recognized as 'foreign' by HLA-DQ immune receptors inside the gut wall -- but only in those carrying the HLA-DQ variants associated with celiac disease."
Gluten-derived proteins also increase the permeability of the intestinal barrier. This makes it easier for microbial transglutaminase and other similar proteins to enter nearby parts of the body, increasing their chances of encountering immune cells that would trigger severe immune responses.
After evaluating antibodies from celiac disease patients, Lerner and Tortsten found that the immune cells left unbound enzymes alone. However, if the transglutaminase complex was bound to a fragment of gluten, the antibodies did not hesitate to activate, even if the bound enzyme happened to be produced by human cells instead of microbes.
The researchers concluded that the immune attacks in celiac disease intended to target microbial transglutaminase bound to gluten fragments. However, the antibodies also targeted human transglutaminase out of a case of mistaken identity.