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What is Celiac disease?

In celebration of my (near) 25th anniversary of my diagnosis with Celiac disease, I thought this would be the perfect venue to introduce this autoimmune disease that is so near and dear to my heart, and additionally update myself on new research in the field.

A trend of gluten-free diets has officially hit the US, however despite the recent explosion of health buffs and rich housewives avoiding gluten, Celiac disease is a genetically bred, serious condition that results from a misinformed immune system. Let me explain…

What is an autoimmune disease?

An autoimmune disease is the result of an overactive immune response against compounds (molecules, proteins, tissues, organs, etc) that are normally present in the body. In other words, it is an attack on the homeland by it’s own citizens. A good example of this phenomenon is Diabetes mellitus type 1 (type 1 Diabetes or juvenile diabetes). The body produces antibodies targeted against insulin-producing cells (islet cells), insulin itself, and other enzymes or phosphatases required for the production of insulin. This results in inflammation and subsequent destruction of insulin-producing beta cells of the pancreas. Insulin is required for regulating fat and carbohydrate metabolism in the body and is provided within the body in constant proportion to remove excess glucose from the blood; therefore, when insulin-producing cells or insulin is targeted for degradation, the levels of glucose in the blood are toxic.

Who is attacking whom in Celiac disease?

Celiac disease results from the interaction between gluten and immune, genetic and environmental factors. Gluten is a protein derived from wheat, barely and rye, and is generally poorly digested in the human upper gastrointestinal tract. Additionally, gliaden is the alcohol-soluble portion of gluten that cannot be digested and the portion that passes through the epithelial barrier of the intestine and interacts with immune cells in the lamina propria. These immune cells are antigen-presenting cells, therefore these cells can present antigen, like gliaden, that can be recognized and targeted by killer immune cells or antibodies against gliaden.

In non-Celiac, these killer cells would not be interested in the gliaden antigen presented to them, and the cells presenting gliaden would be neglected. However, people with Celiac disease have antibodies against gliaden, and upon gliaden antigen presentation anti-gliadin antibodies can recruit killer immune cells (innate immune cells) and induce production of more antibodies against gliaden (adaptive immune cells), subsequently causing chronic inflammation of the small intestine and atrophy of the villa in the small intestine.

Figure 1: New England Journal of Medicine – After digestion of gluten, gliadin peptides induce changes in the epithelium through the innate immune system and, in the lamina propria, through the adaptive immune system. This leads to damaged epithelial cells and villous atrophy.

Symptoms of Celiac result from this immune reaction including:

The innate response (pictured below), or the killer immune cell response, is mediated by the increased production of IL-15, a signal molecule that can induce proliferation of Natural Killer cells (NK cells). NK cells do what you think they do, they hunt and kill. In the small intestine of Celiac patients, after ingestion of gluten, antigen-presenting cells in the intestine presenting gliaden will be targeted and destroyed by NK cells, causing massive inflammation in the intestines – mimicking a bacterial or viral infection in the small intestine.

The adaptive response (pictured below), or the increased production of anti-gliaden antibodies, is mediated by gliaden-specific-CD4+ T cells in the lamina propria. CD4+ T cells are helper cells for the immune system, when an antigen is presented on the surface of an antigen-presenting cell, the CD4+ T cells can recognize this specific antigen. In response to recognizing the antigen, they can talk to B cells that can make more antibodies to increase the recognition of this dangerous antigen and the efficiency of the immune system. Generally the antigens that CD4+ T cells are recognizing are those of bacterial or viral proteins, however people with Celiac disease have CD4+ T cells that recognize gliaden – and this leads to a massive, long-lasting immune response to gliaden.

What are the genetics behind Celiac disease?

Unfortunately for my future offspring Celiac is genetically linked. Specifically, Celiac disease does not occur unless both HLA genes that encode HLA-DQ2 or HLA-DQ8 proteins are present. HLA proteins make up the major histocompatibility complex (MHC) that presents antigens on antigen-presenting cells, those wonderful and necessary immune cells I have previously mentioned.

However, many people carry these specific HLA genes – thus HLA genes that encode HLA-DQ2 and HLA-DQ8 proteins are necessary, but not sufficient to cause disease, and studies show that the contribution of HLA genes to development of the disease is less than 50%. Also, there have been multiple non-HLA genes identified in correlation with Celiac disease, but the correlations are not yet clear.

How are you diagnosed with Celiac disease?

There are two general ways that Celiac disease is diagnosed, duodenal biopsy or serological testing. Duodenal biopsy can identify intracepithelial lymphocytosis (increased immune cells in the intestines) and villous atrophy (loss of villa in the intestinal wall) and is considered the fail-proof method of diagnosis. There are two biopsies, one before the gluten-free diet and one after 6 months of a gluten-free diet. After 6 months of a gluten-free diet the number of immune cells decreases in the intestine and generally there is full recovery of villa.

The serological testing, or the diagnosis of Celiac disease using a test to identify anti-gliaden antibodies (or other antibodies related to Celiac) can range from 90-99% effective, however people without Celiac disease tend to test positive to these tests – therefore, it is difficult to diagnose with the antibody test alone. There are other indicators in the blood as well, you can test folate and iron deficiencies to look for malaborption of metabolites that are a result of atrophied villa in the small intestine.

Can you avoid getting Celiac?

As in most autoimmune diseases, Celiac is more prevalent in women than men, so it pays to be of the male variety. Additionally, if you’re from a European ancestry you’re not lookin’ too good, however Celiac disease has been found in the Middle East, Asia, South America and North America.

More specifically, environmental factors have been linked to diagnosis of Celiac disease. There has been occurrence of gastrointestinal infections, like rotavirus, increasing the risk of Celiac disease in infancy. Also, during breast-feeding introduction of gluten before 4 months of age can increase risk of Celiac disease, however breast-feeding may be more important for protecting against Celiac disease.

What happens clinically in Celiac disease?

The innate and adaptive immune responses described above induce multiple unpleasant symptoms that I have been lucky enough to live with my whole life – but just like any other autoimmune disease, these symptoms vary greatly throughout the population.

Across ages and sexes there are general symptoms of diarrhea, abdominal distention, and failure to thrive. Additionally, older children and adolescents present non-intestinal symptoms such as short stature, neurological symptoms & anemia. In few cases Celiac disease may be presented on the skin as dermatitis herpetiformis.

Treatment is simple, but painful for people who are diagnosed later in life, a gluten-free diet. No more cake and pizza. I spent most of my childhood looking for food in hippy health food stores 20 miles from my house - luckily for me and other Celiac patients, the health buffs & rich housewives like gluten-free diets as well so there are many gluten-free options hanging out at any local Kroger.

Let me know if I didn’t cover a Celic disease questions!


Peter H.R. Green, M.D., and Christophe Cellier, M.D., Ph.D. (2007). Celiac Disease New England Journal of Medicine, 357, 1731-1743

MacDonald, T. (2005). Immunity, Inflammation, and Allergy in the Gut Science, 307 (5717), 1920-1925 DOI: 10.1126/science.1106442

LUDVIG M. SOLLID , GUNNAR MARKUSSEN , JOHAN EK, HALLVARD GJERDE, FRODE VARTDAL , AND ERIK THORSBY (1989). Evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer New England Journal of Medicine

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Reader Comments (8)

What is it about the autoimmune response that can have neurological effects?

Also, are there any ill effects that are not autoimmune-related resulting from the fact that no one can digest gliaden?

October 31, 2011 | Unregistered CommenterSarah Scoles

That is an interesting question. I'm not sure we have the answer to that yet... however I could imagine two scenarios - 1) Correlation - genetic predisposition of Celiac is linked to genetic predisposition to neurological disorders or 2) Causation - chronic inflammation of the gut caused by Celiac can effect hormone balances thus puberty & growth is effected (late puberty is seen in young Celiac patients), or something like immunologically privileged sites (like the brain) can be infiltrated by an imbalanced body - something crazy like an imbalance in gut bacteria can induce neurological changes (I wrote a post about these two things interacting a while back). I really don't know though!

Your second question is also a toughy but a goody! There is such thing as non-Celiac gluten sensitivity (NCGS) or gluten-related disease (GRD) - however, I'm not sure I actually believe in these two diseases, there's a lack of literature in non-Celiac gluten intolerance.

It looks as though if you don't have the corresponding HLA genes that coincide with Celiac, then there's not a particularly high risk of reacting to gliaden.

November 1, 2011 | Unregistered CommenterBrooke N.

Great article! How does a viral infection trigger celiac disease?

November 1, 2011 | Unregistered CommenterAnonymous

Biesiekierski J. R., E. D. Newnham, P. M. Irving, J. S. Barrett, M. Haines, J. D. Doecke, S. J. Shepherd, J. G. Muir, and P. R. Gibson. 2011. Gluten Causes Gastrointestinal Symptoms in Subjects Without Celiac Disease: A Double-Blind Randomized Placebo-Controlled Trial. The American journal of gastroenterology. 1-7.

This was a great paper out earlier this year about gluten intolerance. From my understanding, we can now say that gluten intolerance is real, but we still have no clue what is going on.

November 1, 2011 | Unregistered Commentergfpumpkins

I have tested negative for Celiac twice, but I have gluten intolerance. I get hives, migraines, and feel drunk when ingesting gluten. I have been entirely gluten-free (except for minor accidental ingestions) for a year and a half, and my health has definitely improved, my head is clearer, my eyes focus better, and I've lost 40lbs. But my tests all say I don't have Celiac.

November 2, 2011 | Unregistered CommenterDaphyn

Great post, thanks.

> neurological effects

The first sign I get that some gluten has slipped into my system is that my emotions become unbalanced. For a small amount I get irrationally angry and for a larger amount I become very depressed. So for me there is some form of neurological component. It is these mood swings that inform me that something is wrong, so not placebo. A day later the digestion problems start.

>But my tests all say I don't have Celiac.

None of the tests are 100% accurate, so this does not mean that you don't have celiac disease.

November 2, 2011 | Unregistered Commentersystemicplural

Great background about Celiac Disease, which most people confuse with wheat allergy or gluten sensitivity. Understanding the key immunological mechanisms that promote this disease, will likely improve our ability to not only treat the disease, but to aslo improve our diagnostics-as already mentioned by some commenters, that current tests are not 100% accurate.

@anonymous: I am an immunology PhD student studying inflammation and to help answer your question: it may be that viral infections do not directly cause celiac disease, as this is an autoimmune disorder, but that such infections enhance the production of pro-inflammatory cytokines that, if this occurs in the gut of a Celiac patient, he/she is unable to properly regulate the gut inflammation and it may lead to tissue destruction and symptoms described above.

If you are interested in learning more about the immunology behind the disease and want to dive into exciting the data from the latest published research papers in the fields of human health, immunology and disease, I encourage you to check out my Immunology Research Blog@ http://escapinganergy.blogspot.com/

November 4, 2011 | Unregistered CommenterHeather

Very nice article. Is there any way to prevent it from infecting other people?
Medical Cannabis Doctor

October 30, 2013 | Unregistered CommenterMedical Marijuana

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