As you stroll through your local grocery store, you may have noticed an increase in gluten-free products over the years. Perhaps you've even tried a few yourself. Although some might view this as the latest diet trend, the surge in availability of products is a welcome relief for those living with celiac disease. The reality is celiac disease is an autoimmune condition impacting one in every one-hundred people (Celiac Disease Foundation, n.d.). What is actually happening in the bodies of people with celiac disease? This article will discuss what gluten is, the molecular damage that occurs when consuming gluten, the immune response to this damage, and the genes involved in celiac disease.
What is Gluten?
Gluten is a mesh like structure that forms from wheat, barley, and rye when gliadin protein and glutenin protein join together in water (Gasbarrini & Mangiola, 2014). The mesh is what gives gluten dough its stretchy consistency. Research has identified gliadin protein as the part that is toxic to those with celiac disease (Gasbarrini & Mangiola, 2014).
What Happens When Someone With Celiac Disease Ingests Gluten?
In a healthy person's intestines, there are tight junctions between the small intestinal cells (enterocyte cells) that form a protective barrier (Parzanese et al., 2017). Imagine these cells tightly packed in a row, guarding the small intestine. However, in people with celiac disease, fragments of indigestible gluten, specifically gliadin, can penetrate this barrier. This triggers the release of a chemical called zonulin, which loosens the tight junctions between the cells, allowing more gliadin fragments to enter and accumulate. The accumulation of gliadin fragment cells triggers an immune response, where lymphocytes, a type of immune cell, attack the cells containing gliadin (Gasbarrini & Mangiola, 2014). Essentially, the body starts attacking itself.
Immune Response
The attacking lymphocytes is only the beginning of the immune response. Damaged intestinal cells release a substance called tissue transglutaminase (tTG), which can alter the gliadin fragment (Gasbarrini & Mangiola, 2014). The altered fragment is then shown to the immune system by the body's human leukocyte antigen (HLA) molecules. HLA molecules help the immune system by presenting small pieces of foreign substances to the body called antigens (CD Genomics, 2023). In the case of celiac disease, the modified gluten is the antigen. When HLA connects with the modified gluten, helper T cells get involved. Helper T cells release inflammatory molecules that activate killer T cells that destroy the intestinal cells. Additionally, helper T cells activate mature B cells which release antibodies against tissue transglutaminase.
The end result of this multi-step immune system reaction in someone with celiac disease is that more and more intestinal cells get damaged, the villi in their intestines become flattened, and their body mounts an autoimmune response to ingesting gluten. The villi in the small intestine are there to help absorb nutrients. When someone with celiac disease has flattened and damaged villi, it impairs their ability to absorb nutrients properly (Gasbarrini & Mangiola, 2014).
Genetics
Having a mutation on the Human Leukocyte Antigen (HLA) gene, specifically on the alleles of HLA-DQ2 and DQ8, makes someone more genetically predisposed to have celiac disease (Gasbarrini & Mangiola, 2014). A mutation on the alleles of HLA-DQ2 and DQ8 allows the HLA molecules in the body to bind to the modified gliadin and present it to the immune system. It is important to note that this genetic factor alone does not fully cause celiac disease. Other factors, such as environmental triggers, also play a role in the development of the condition (Gasbarrini & Mangiola, 2014).
Conclusion
There is much more happening beneath the surface for someone with celiac disease. Even a small amount of gluten ingested by those with celiac disease can trigger the autoimmune cascade discussed earlier, leading to serious health complications. The only treatment options for those with celiac are to adhere to a gluten-free diet and to be diligent about avoiding cross-contamination.
The Month of May is dedicated to Celiac Awareness. It's an ideal time to explore available resources for your loved ones with celiac and recognize that eating gluten-free is not a lifestyle choice for them, rather an important step in managing a serious autoimmune disease.
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CD Genomics. (2023, December 23). Human Leukocyte Antigen Molecules and HLA
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Celiac Disease Foundation (n.d.). What is Celiac Disease?
Gasbarrini, G., & Mangiola, F. (2014). Wheat‐related disorders: A broad spectrum of
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Häggström, M. (2022). Histopathology of villous atrophy in celiac disease [Photograph].
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