272019Aug
What Triggers Celiac Disease: Reasons Beyond Gluten

What Triggers Celiac Disease: Reasons Beyond Gluten

The answer to what triggers celiac disease is a combination of factors including genetics, gluten exposure, internal gut environment, and external environmental factors. We will explain each in greater detail and how these contribute to developing celiac disease.

Celiac disease is an autoimmune disease that is a reaction to eating gluten, where an immune response is triggered that attacks the small intestine and damages the villi that line the small intestine. When the villi get damaged, nutrients cannot be absorbed properly into the body.

What triggers celiac disease: genetics

People with celiac disease have immunologic agents known as human leukocyte antigens (HLAs)

One such antigen, HLA DQ2, plays an important role in gluten intolerance/celiac disease. Each HLA subtype is capable of recognizing and binding to a specific foreign protein. This HLA and foreign-protein-binding-pair form what is known as a “complex.” The creation of this complex signals a specific type of white blood cell (a T Cell) to initiate an immune response.

In people with celiac disease, HLA DQ2 specifically binds to gluten, and the resulting complex, then triggers T cells located in the small intestine, which leads to inflammation.

What triggers celiac disease: external environment

Several environmental factors have been proposed, including exposure to toxic metals and toxic chemicals; infectious agents, including bacteria and viruses. Significant stress and trauma have also been identified in many cases. We can reasonably conclude that autoimmune diseases are caused by a combination of factors.

What triggers celiac disease: gluten exposure

Why gluten?

As gluten is not digestible by humans, our enzymes can only break gluten apart into large fragments. Left on their own, these large gluten fragments wouldn’t cause any problems. They’d be excreted along with the other unusable parts of the food we eat. But in genetically susceptible individuals, in combination with certain environmental factors, the interaction of gluten fragments with tTG launches an immunological chain reaction.

tTG or tissue transglutaminase is a common enzyme found in many locations throughout the body including the cells residing below the inner lining of the small intestine.

In the small intestine when tTG interacts with gluten protein fragments, this causes a biochemical change—deamidation—that primes gluten fragments to set off a widespread immune response.

tTG and HLA: A perfect storm

HLA DQ2s and DQ8s will not normally interact with gluten fragments. But when the enzyme tTG changes a gluten fragment in the process of deamidation, the modified gluten protein structure causes it to be snatched up by HLA DQ2 and DQ8 antigen-displaying proteins. In a series of responses, your body now reacts to the gluten proteins as if they were a threat.

What triggers celiac disease: internal gut environment

A major research question asks: why do only a small proportion of people who are genetically susceptible to gluten intolerance develop symptoms? Approximately 40% of individuals have the HLA DQ2 and HLA DQ8 genes, but only 1% of them will develop celiac disease.

Why is that?

The key to understanding this difficult question is that genetics is not the only important factor. How the genetic sequence is expressed is very important, but the internal environment of the individual also represents a critical dynamic.

Why one person develops celiac disease and another won’t even if both are genetically susceptible.

Person A and person B may have an identical genetic sequence. Both may have sequences coding for antigen-presenting HLA DQ. But only person A will manufacture DQ2 or DQ8 proteins and possibly develop gluten intolerance, all owing to person A’s internal molecular environment.

Why does this happen? This goes back to tTG.

How do gluten proteins in the small intestine come in contact with tTG, which is contained within certain cells in the lamina propria, which is protected by the epithelial barrier—a sort of “wall” that is supposed to prevent foreign materials from gaining access to the cells and tissues of the host? Environmental triggers.

lamina propria image

The intestinal epithelium “wall”


Bacterial and viral infections cause immune responses and inflammatory reactions that can break down structures in the small intestine; leading to increased permeability (the “wall” becomes more permeable). Similarly, a sufficiently high fever, prolonged use of antibiotics or NSAIDs, poor diet, excessive alcohol intake, stress, and yeast overgrowth can lead to increased permeability. Infection, inflammation, and wound healing may also cause the release of tTG from cells in the lamina propria. All of these things can contribute to increased gut permeability allowing gluten protein fragments to come into contact with the now-available tTG.

Going back to the previous statement that person A’s internal environment is a contributing factor to developing CD or not. Person A’s internal environment depends to a large extent on his or her external environment, as just mentioned. Has the person experienced frequent infections or fevers? Have they used antibiotics or NSAIDs for an extended period of time? Do they have a poor diet? If any of these are true, this could be the contributing factor that leads person A to develop celiac disease or gluten intolerance while person B doesn’t.

Another common question related to gluten exposure relates to the length of exposure. Will the amount of time I’ve been exposed to gluten increase my chance of developing additional autoimmune diseases?

The amount of time a genetically predisposed individual is exposed to gluten has been shown to be directly correlated with the risk of developing additional autoimmune diseases. A large multicenter trial conducted in Italy studied more than 900 patients with celiac disease. Overall, the prevalence of autoimmune disorders in this group was 14%, compared to a prevalence of 2.8% in 1268 controls. Additionally, the prevalence of autoimmune diseases increased in patients with celiac disease the longer celiac disease remained undiagnosed or, in other words, the longer these patients were exposed to gluten.

For example, in patients in whom celiac disease was diagnosed before the age of two, only 5% of these individuals had an associated autoimmune disorder. In marked contrast, in patients who were older than age 20 before they received a diagnosis of celiac disease, 34% had an associated autoimmune disease. Of the study patients with celiac disease, 36 (4%) also had type 1 diabetes, 32 (3.5%) had dermatitis herpetiformis, 12 (1.3%) had mixed connective tissue disease, 12 (1.3%) had autoimmune thyroiditis, 10 (1.1%) had autoimmune hepatitis, and 4 (0.4%) had cerebellar ataxia. Overall, the prevalence of autoimmune disease in young adult and adolescent patients with celiac disease is much higher than in the general population.

While cutting gluten from the diet is a main step in healing from celiac disease, it may not be the only contributing factor.  When putting together the complete picture of what triggers celiac disease, a combination of factors should be considered. Often times following a gluten free diet is not enough to eradicate your symptoms, but if you can identify the external and internal influences your recovery will be more successful.


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