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Celiac Disease

Logan Stone

What is Celiac Disease?

 

Celiac disease (CD) is a disease in which the body cannot break down gluten and begins an autoimmune response against gluten (1). Gluten is a complex protein that is commonly found in wheat, rye and barley products. Now, gluten is comprised of a mixture of storage proteins, but the key protein that causes a majority of the symptoms of CD is gliadin (2). Giladin proteins can bind to dendritic cells, which will present this dendritic-giladin complex to body’s immune cells. The human body contains immune cells, CD4+ and CD8+ T cells that have receptors for gliadin (3). When a patient with CD consumes a gluten product, these levels of gliadin will begin to rise in the intestinal and digestive tracts. This creates an overstimulation of these gliadin receptors on the CD4+ and CD8+ T cells in these areas of the body. The cells will trigger a cellular pathway that invokes an autoimmune response (2). This will cause the patient to experience chronic diarrhea, weight loss, abdominal distention and even anemia (4). The severity of these symptoms can vary from patient to patient and many people may never realize they have CD. Its proven by studies that 1 in 100 people worldwide have CD, making this one of the common food intolerances (4).

 

What is the difference between Celiac Disease and Gluten Intolerance?

 

The symptoms of CD and gluten intolerance are very similar. Patients with either one will experience pain in the gastrointestinal area caused by inflammation, which can also lead to diarrhea and abdominal distension (5).To clearly define gluten intolerance, the gluten intolerance group (GIG), has derived the term non-celiac gluten sensitivity (NCGS) to replace the general term of gluten sensitivity (5). Since NCGS and CD result in nearly the same symptoms and are triggered by the same protein, its expected that the cellular pathways that causes these symptoms are also similar. The main difference between CD and NCGS is the autoimmune responses that are only seen in CD. Figure 1 demonstrates how the cellular pathways of CD and NCGS overlap and the small difference between the two.

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Celiac_signal_diagram.png

Cellular Pathway

 

Figure 2: This is the possible mechanism to the underlying cause of CD and NCGS. The figure also demonstrates the suspected difference between the two diseases. Gluten passes through the intestinal lumen and enters the lamina propia, where the gluten proteins are broken down by tissue transglutamase. Although in patients with CD or NCGS, not the entire protein is degraded and a sub-protein, giladin, is left. Giladin can then bind to the HLA DQ-2 receptors on Androgen Presenting Cells (APC). The APC presents giladin to CD4+ T cells. From here the cellular cascade is initiated and an immune response is triggered in the intestines.  The Th0, Th1, and Th17 lymphocytes all produce cytokines that causes inflammation in the small intestine, they also cause villous atrophy, and even crypt hyperplasia. This causes patients to experience abdominal pain, bloating and even diarrhea.  These cellular responses occur in patients with both diseases but the last response in the diagram, involving antibodies, is believed to occur only in patients with CD. In this last response, the Th2 lymphocyte presents giladin to the B-memory T cells of the immune system. These cells create antibodies specific to giladin. This means the next response to gluten may occur faster and have a more sever effect on the patient (1) .

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Testing

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Currently there are only 2 types of testing for CD. The first test a doctor will recommend would be Serology Test, which looks for the aintgiladin antibodies in the patient’s blood.  This is the main test for CD since it’s quicker and much more cost effective than the second exam. The second exam would be a genetic analysis to look and see if the patient has the genes for CD. This genetic analysis can be costly and take several weeks or even months (6).

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Treatments

 

The currently, only known treatment for patients with CD and NCGS is a gluten free diet. For some, a diet change can be difficult but working with a dietitian and other patients with CD can make the transition a lot easier. In today’s world, there thousands of recipes without gluten and many restaurants and shops now carry gluten free options.  It may be odd to some that a simple protein can have such an effect on the body. Although studies how shown that diagnosed patients with CD see regression of their symptoms in the first couple weeks of being on a gluten free diet. Most children who have some intestinal damage from CD will heal completely after following the diet (7). The pathway for CD is nearly understood and hopefully in the future someone in the field of medicine will design an enzyme that will help patients with CD or NCGS breakdown giladin, so they can be “cured” of CD.

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Literature Cited

 

  1. Wijmenga, C., Trynka, G., & van Heel, D. A. (2010). A genetic perspective on celiac disease. Trends in Molecular Medicine, 16(11), 537-550. doi:10.1016/j.molmed.2010.09.003

  2. Mazzarella, G. (2015). Effector and suppressor T cells in celiac disease. World Journal of Gastroenterology : WJG, 21(24), 7349-7356. doi:10.3748/wjg.v21.i24.7349

  3. Piechota-PolaÅ„czyk, A., SaÅ‚aga, M., & Huk, I. (2015). T cell-activated signaling pathways and locally produced cytokines as potential targets in celiac disease. Current Drug Targets, 16(3), 226-232.

  4. Deutsch, H., Poms, R., Heeres, H., & van der Kamp, J. (2008). In Arendt E. K., Dal Bello F. (Eds.), Gluten-free cereal products and beverages. San Diego: Academic Press.

  5. Celiac disease, non-celiac gluten sensitivity or wheat allergy: What is the difference? (2017) Retrieved from https://gluten.org/resources/getting-started/celiac-disease-non-celiac-sensitivity-or-wheat-allergy-what-is-the-difference/

  6. Celiac disease testing (for health care professionals) | NIDDK. Retrieved from https://www.niddk.nih.gov/health-information/diagnostic-tests/celiac-disease-health-care-professionals

  7. Ronit Rose. Essential of celiac disease and the gluten-free diet. Chicago, Il: University of Chicago Celiac Disease Center.

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