Blood Testing for Celiac Disease

When you are tested for celiac disease, you almost always have blood tests drawn looking for antibodies to tissue transglutaminase (tTG) as well as endomycial antibodies (EMA). These are tests of a particular kind of antibody, also called immunoglobulin, which your body may be making in reaction to parts of the intestinal lining.

What exactly are immunoglobulins? Immunoglobulins or antibodies are a part of the body’s defense system. They are made by a type of white blood cell called a B cell. There are 4 main kinds of immunoglobulins.

IgM is what the B cells make when they first meet up with a virus, bacteria or other toxin and are trying to fight off the infection. IgM is found in the blood.
IgG is made the next time the body is exposed to a specific virus or bacteria. IgG can be measured to show that a person had a specific infection in the past, which usually means they are immune to that infection. For example, women can be tested for immunity to German measles before they get pregnant. IgG is found in the blood and tissues.

IgE is made in response to something that causes an allergy in people susceptible to allergies. Someone who has hay fever will make IgE to pollen, grass, mold, pet dander, and/or other specific materials that are called antigens. IgE combined with the antigen causes cells to release chemicals which lead to the symptoms of an allergy, like sneezing and a runny nose. IgE is found in mucous and small amounts can be measured in blood. The levels are higher in allergic individuals.

IgA is a first line of defense, in that it is found in the nose, eyes, lung and digestive tract. These antibodies attempt to stop a virus or bacteria from getting into the body. In celiac disease, IgA is mistakenly attacking the intestinal lining. In dermatitis herpetiformis, it is deposited in skin cells, where it does not belong. Because of the production of specific types of IgA in celiac disease, these antibodies can be measured to help diagnose the disease.

Some people do not have normal amounts of IgA in their bodies. This is a type of lowered immunity, although it is not severe. It is the most common type of immunodeficiency, affecting, for example, between 1:300 (1:800 people of European descent). However, individuals with low amounts of IgA are 10 to 20 times more likely to have celiac disease. Looking at it another way, it is estimated that at least 2.6% of people with celiac disease have low amounts of IgA.

This poses an obvious problem. It means that people with low IgA levels may test negative for IgA anti-tTG and EMA, the test used to screen for celiac disease. While there is an occasional person who does have positive tests despite very low IgA levels, most people with this deficiency test negative.

If a doctor suspects celiac disease and the screening tests are negative, there are a number of ways to proceed. Some may then measure the patient’s immunoglobulin levels. If IgA deficiency is present, IgG antibodies to tTG and EMA can be checked. Some studies have shown that these tests are not as conclusive or accurate as the IgA tests. If the suspicion of gluten intolerance is very high, intestinal biopsies should still be done and will show abnormalities if the person has celiac disease.

There are two ways to approach the problem of low IgA in celiac patients. One way is to measure serum IgA levels at the same time as a-tTG and EMA. People with low IgA and negative antibody tests for celiac disease would then be tested with a different blood test, such as IgG antibodies. The other way is to only measure total IgA in people suspected of celiac disease who have negative IgA antibody tests. If their IgA is low, other tests would then be done.

Obviously, a very good blood tests to screen people who are IgA deficient for celiac disease is needed. There is one test that may be able to do that. It measures IgG antibodies against “deamidated gliadin peptides.” Gliadin is a part of gluten that people with celiac disease react to. Tests for antibodies against gliadin itself have not been accurate. However, when the gliadin is treated a specific way, antibodies against the treated gliadin are more likely to be found. This test is called IgG-anti-dGli.

Some studies have shown that IgG-anti-dGli may not only be an accurate test in people with low IgA, but also in people with normal levels. The test is not readily available or used routinely at this point. It is possible that in the future, this may be one of the tests used to screen all people for celiac disease and to monitor response to a gluten-free diet.

If you and/or your doctor are very suspicious that you have celiac disease, and the standard tests are negative, you should ask if your IgA has been measured. If it hasn’t been, it should be. If it is low, other blood tests should be done, and biopsy should still be considered.

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References:
Valletta, E, Fornaro, M, Pecori, S, Zanoni, G. Selective Immunoglobulin A Deficiency and Celiac Disease: Let’s Give Serology a Chance. Journal of Investigative Allergology and Clinical Immunology 2011; 21(3): 242-244.
Villalta, D, Tonutti, E, Prause, C, et al. IgG Antibodies against Deamidated Gliadin Peptides for Diagnosis of Celiac Disease in Patients with IgA Deficiency. 2010 Clinical Chemistry 56;3: 464–468.
Porter, RS, Kaplan, JL, editors. The Merck Manual Home Health Handbook. 2009. Merck & Co., Inc. Whitehouse Station, N.J.