Testing for Celiac Disease and Non-Celiac Gluten Sensitivity

testing for celiac disease
Celiac disease is a debilitating ailment, producing many complications that can prevent us from living our lives to the fullest. It is a disease that can lead to irreparable consequences to our whole body, most especially our intestines. As is the case with almost all diseases, prevention is much easier than cure. However, patients won’t readily subject themselves to gluten-free diets unless they are certain that they already have the disease or are at risk for it. More importantly, most people believe that they need to manifest symptoms (especially those related to the gastro-intestinal tract) before they even consider the likelihood of having celiac disease or gluten sensitivity. Thus, it is important to find means to identify gluten sensitivity in a patient without having to wait for symptoms.

Screening Tests for Celiac Disease

The diagnostic test of choice in detecting celiac disease is through the measurement of circulating antibodies within the patient’s blood. This is performed before the patient is subjected to a gluten-free diet because the patient does need some gluten intake to at least elicit the response of increased antibody titers. Nonetheless, it should be remembered that no screening test is perfect. Identifying villi atrophy on the patient’s intestinal wall is still the gold standard for diagnosing the illness as celiac disease. This is done through intestinal biopsy, the results of which should be considered alongside the patient’s response to gluten-free diet.

Antibodies

Before we can truly understand Gluten Sensitivity and the pathology of celiac disease, we have to be clear about the basic function of the immune system and why it can cause damage to our own bodies. First, we recall what an antibody is and what its purpose is. An antibody is an immunoglobulin which is produced by our body’s plasma cells. These plasma cells are the cells which the body or the immune system uses to both identify and neutralize foreign bodies such as microorganisms (viruses, bacteria) and in certain cases food products and medical devices. Antibodies are similar to specialized soldiers with the unique purpose of identifying a specific foreign target which is called an antigen. An example of an antigen is a component of the bacterial cell wall or gluten. The antigen has a specific structure, a paratope, which can latch onto some structure or other in the foreign body. Once latched on, the plasma cell can either signal for other portions of the immune system to attack the foreign object or it can destroy the antigen itself.1

Medical Relevance

Both the attending physician and patient should know how the body functions and, in particular, how our immune system responds to any and all threats that we are exposed to. Knowing about antibodies can also help in medical diagnosis. Detecting a specific type of antibody reveals the presence of a particular disease in a patient quite ahead of clinical or physical manifestations of the disease.

Often times, there are viruses which have similar early manifestations which are non-specific. Examples are fever, colds, cough, diarrhoea, constipation, vomiting and nausea. Given how nonspecific these are, one needs to detect the antibodies involved to give the appropriate medical treatment.

For example, elevated levels of certain immunoglobulins can help doctors identify the cause of liver damage in certain patients whose diagnosis is unclear, whether caused by alcoholic liver cirrhosis or viral hepatitis.2

In the case of patients with non-specific symptoms and the doctor would like to admit or rule out a condition such as Gluten Sensitivity, the key is to check on the patient’s antibody titer for anti-gliadin.

Anti-Gliadin

A patient produces anti-gliadin antibodies as a response to gliadin. Gliadin is a prolamin found in wheat. If a patient produces these antibodies, the immune system will readily launch an attack on the foreign body and cause a reaction that may or may not produce readily-apparent symptoms. These are the same inflammatory cells that are readily activated the moment the patient ingests any food with gluten in them. The indicated treatment then is to subscribe to a gluten-free diet.

Antibody Tests Available

There are two classes of antibody blood testing, those that are anti-gluten and blood tests which targets the patient’s own cells (the anti-self antibodies). Classified under “anti-gluten” antibodies are IgG and IgA that are anti-gliadin. These are otherwise known as anti-gliadin immunoglobulin (antibody) G and A. Anti-tissue transglutaminase IgA and anti-edomysial IgA are both classified under “anti-self” antibodies.

Each test varies in sensitivity and specificity in identifying and predicting the presence of the disease in the individual. After all, no single diagnostic test for gluten sensitivity is completely reliable. There is always room for error.

Medical technologists also admit to the possibility of a “false negative” antibody test result. This means that the test may have concluded that the patient has no anti-gliadin antibody and thus conceals the reality that anti-gliadin IgG is present or that the patient really has gluten sensitivity. A classic example of this false negative test is if the patient has IgA deficiency and the test is specific for anti-gliadin IgA in the patient’s blood. In this disease, the patient’s IgA is low, which gives a false reading for anti-gliadin IgA levels.

Anti-gliadin Antibodies

These are IgG and IgA which are made to specifically to identify a small part of the gluten protein, called gliadin, in wheat breads and products. This was first proposed as early as the 1970s in order to aid in identifying if the patient has celiac disease. Anti-gliadin IgA is highly specific, while Antigliadin IgG is highly sensitive. With the combination of both antibody tests, it is possible to have a reliable screening test for celiac disease.3

Non-Celiac Gluten Sensitivity

There are instances when tests yield negative results and yet patients suffer from symptoms after ingestion of gluten. These patients are proven to be non-celiacs and not allergic to wheat either.

Non-celiac gluten sensitivity comprises those patients who have negative test results and yet feel better the moment gluten is removed from their diet. This means that they tested negative for IgE test for wheat, therefore proving that their allergy is not specific for wheat. This also means that the patient had a negative test result for both screening tests for celiac disease.

Individuals with non-celiac gluten sensitivity cannot tolerate gluten and experience similar symptoms to celiac disease. These patients also show no intestinal damage similar to those found in patients with celiac disease. Research suggests that individuals with non-celiac gluten sensitivity experience a reaction due to their innate immune system. This is in contrast to the adaptive immune system which produces auto-immune diseases or cases of allergic reaction.

Innate Immune Response

Humans are naturally born with an immune system which produces an innate response to foreign objects. Unlike the adaptive immune response, innate immune response is not specific to a certain disease entity or foreign object. This kind of response is similar to a soldier who is prepped to fight any and all invaders regardless of which nationality they are.

They might be less efficient in comparison to more specialized cells, but the innate immune response exists in order for the body to send an immediate response defence “team” to limit the damage of the foreign body whilst the adaptive immune system examines the foreign substance and creates a more accurate and precise response to the invasion.

The adaptive immune response has something called an immunological memory. This means that after the initial contact with the foreign organism, the adaptive immune response will be ready for a secondary invasion even if the time interval between microorganism invasions is at least a decade. Unfortunately, the innate immune system does not have an immunological memory. This is why the innate immune system cannot render a specific and highly efficient attack against invading organisms. However, this also means that the innate immune system cannot assault self-tissue or our own cells. Hence it plays no part in autoimmune diseases.

The components of celiac disease are antigen-specific. This includes tissue-transglutaminase, de-aminated gliadine antibodies, endomysium and other anti-gliadin antibodies. Since these are antigen-specific, if one’s own, organic or self-tissues have similar components to the antigen which the immune cells are supposed to attack, then the antibodies will latch on to them and destroy them. This leads to intestinal damage or enteropathies, because the inflammatory cells attack the intestinal tissues of the patient’s body as well as other cells of the body.

This is different from non-celiac disease which is not antigen-specific and thus does not cause the same physical damage doctors look for when the intestinal walls are biopsied.

Symptoms of Non-Celiac Gluten Sensitivity

The aforementioned non-celiac gluten sensitivity symptoms similar are to those of celiac disease. This makes it hard to differentiate either syndrome. They share similar intestinal and extra-intestinal symptoms such as headache, joint inflammation, numbness of the limbs and impaired cognition. Typical to innate immune response, the symptoms usually appear within hours or days after the ingestion of gluten. In celiac disease however, these symptoms continue for weeks to months after the patient’s last gluten intake.4

Since the innate immune system has a less specific skill set (or pattern match), this means their capacity to do damage is not as great as when the adaptive immune system is at work. This is why non-celiac gluten sensitivity is recognized with clinically less severe symptoms in comparison to celiac disease. Since there is no intestinal damage or destruction of the self-tissues, this means that tissue markers such as tissue-transglutaminase, de-aminated gliadin and endomysium antibody levels are all depressed in comparison to the values found in celiac disease. This also means that biopsy will not reveal increased mucosal permeability which is one of the pathognomonic signs of celiac disease. Due to these vital differences, the patient can have negative results in the biopsy, the IgE skin test and blood tests, but notice a considerable improvement in their symptoms after the removal of gluten from their diet.

Show 4 footnotes

  1. Litman GW, Rast JP, Shamblott MJ, Haire RN, Hulst M, Roess W, Litman RT, Hinds-Frey KR, Zilch A, & Amemiya CT (January 1993). “Phylogenetic diversification of immunoglobulin genes and the antibody repertoire”. Molecular Biology Evolution 10(1): 60–72.
  2. Rhoades RA& Pflanzer RG (2002). Human Physiology (4th ed.). London: Thomson Learning.
  3. Volta U, Cassani F, De Franchis R, et al. (1984). “Antibodies to gliadin in adult coeliac disease and dermatitis herpetiformis”. Digestion 30 (4): 263–70.
  4. Sapone, A., Bai, J.C., Ciacci, C., Dolinsek, J., Green, H.R. Fassano, A., et. al. (2012). Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Medicine, 10, 10: 13.