Approximately 1 in 100 people can experience significant damage to their internal organs from consuming even trace amounts of gluten.
The domino effect of immune responses can be traced back to its origins. genetic rootsa large number of contributing factors are also involved, making it difficult to precisely map the sequence of events that trigger a response to gluten.
An international team led by scientists at Canada’s McMaster University used transgenic mice to identified key roles It is played by the very cells that make up the lining of the intestines, and represents an important stepping stone that could lead to new treatments.
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Celiac disease is essentially an autoimmune disease caused by the presence of a group of structural proteins known as gluten in the intestines.
eat almost anything Anything made with wheat, barley, or rye – meaning most baked goods, breads, and pasta – people in that condition There is a risk of bloating, pain, diarrhea, constipation, and possibly reflux and vomiting.
Currently, the only way to avoid symptoms is to avoid the foods that cause them.
“The only way celiac disease can be treated today is to completely eliminate gluten from the diet.” say Elena Verdu, a gastroenterologist at McMasters;
“This is difficult to do, and experts agree that a gluten-free diet is insufficient.”
About 90% of people diagnosed with this condition have a pair of genes that encode proteins called. HLA-DQ2.5. Of the remaining 10%, most have a similar protein called HLA-DQ8.
As well as other types of “HLA” (or human leukocyte antigen) Proteins, proteins hold pieces of fallen invaders in the air like creepy trophies. classes of immune cellswarning other defense organizations to be on guard.
In the specific case of HLA-DQ2.5 and HLA-DQ8, the proteins are shaped to hold clumps of gluten peptides that are resistant to digestion and tell killer T cells to go hunting.
Unfortunately, these instructions are not the clearest at distinguishing between threats and similar-looking substances in our bodies, meaning those with the gene are at risk for a variety of autoimmune conditions. Masu.
not all However, people who express either HLA-DQ2.5 or HLA-DQ8 develop immune disorders like celiac disease.
To do this, torn pieces of gluten must first be transported through the intestinal wall. transport enzymes It binds to the peptide and changes it in a way that makes it more recognizable.
The cells of the intestinal wall are responsible for releasing this transport enzyme into the intestine, so they clearly play an important role in the early stages of the disease.
They also Express a family of proteins It includes HLA-DQ2.5 and HLA-DQ8 and is normally regulated by the inflammatory response in the intestine.
What is not clear is how this staging area in patients with celiac disease actually functions within the condition itself.
To focus on this important link in the linkage, the research team investigated the expression of key immune complexes in intestinal lining cells from treated and untreated celiac disease patients and in mice carrying the human gene for HLA-DQ2. Double checked. 5.
They then used mouse intestinal cells to create functional biological models of the intestine called organoids and exposed them to proinflammatory substances and digested, intact gluten to study the expression of immune proteins up close.
“This allowed us to narrow down the specific cause and effect and prove exactly whether and how the reaction occurs.” say Tohid Didar, biomedical engineer at McMasters;
This suggests that the cells lining the intestine are not just passive bystanders suffering collateral damage in a misguided effort to remove gluten from the body, but are an important factor in the process of being broken down by gut bacteria. A mashup of gluten fragments was presented and revealed to be an important factor transporting gluten. The enzyme acts directly on gluten-specific immune cells.
Knowing the types of tissues involved and how they are enhanced by the presence of inflammatory microorganisms can provide researchers with a new list of targets for future treatments, potentially reducing discomfort for millions of people around the world. You may be able to enjoy a gluten-filled pastry or two without feeling .
This research Gastroenterology.
A previous version of this article was published in August 2024.
