Celiac disease is a so-called, “autoimmune disease” that
impacts an estimated one percent of the population. An auto-immune disease is caused by an
individual’s immune system attacking its own tissue. Other examples of diseases that fit this classification
are multiple sclerosis (MS), pemphigus, rheumatoid arthritis and systemic lupus.
In Celiac disease, the tissue that is impacted involves the
microscopic villi that line the lumen of the small intestine. These structures provide the surface area through
which digested nutrients are absorbed (see image below). The patient with celiac disease presents with
unexplained loss of weight and fatigue, anemia and constipation for example. The destruction of these highly complex
structures is irreversible; if, this condition is left untreated, it can be deadly.
The trigger for this auto-immune response is the presence of
gluten - a protein found in wheat and related plants. Gluten is a protein that is prevalent in
Western diets. In addition, research
studies have demonstrated that the agent (antigen) that induces the autoimmune
response is not the intact gluten protein but the protein after it is modified
by the enzyme transglutaminase 2 (TG2) within the small intestine. It seems that in normal tissues, although TR2
is an abundant enzyme, it exists primarily in the inactive state.
Chaitan Khosla and his colleagues at the University of California
at Stafford have recently demonstrated that there is a cellular enzyme protein
57 (ERp57) that inactivates TG2.
Normally, ERp57 is involved in the process of protein folding within the
cell. Furthermore, it has been
established that ERp57 inactivates TG2 outside the cell within the
extra-cellular environment. These data
suggest that the etiology of celiac disease may relate to the functionality of
ERp57.
These findings are significant; for, a more detailed understanding
of the biological chemistry of celiac disease may open avenues of therapy that
have heretofore remained elusive.