Blood Tests for Celiac Disease

A simple blood test is usually the first step in the diagnosis

doctor looking at vial of blood

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There are simple blood tests that can aid in the diagnosis of celiac disease. Celiac disease is an autoimmune disorder in which the immune system regards gluten (found in wheat, barley, rye, and other cereal grains) as a threat. Whenever gluten is eaten, the immune system will produce proteins called antibodies—also known as immunoglobulin (Ig)—to fight the presumed threat. The blood tests are designed to detect specific antibodies associated with celiac disease. Elevations in these indicate an abnormal immune reaction to gluten.

Although useful, blood tests alone cannot diagnose celiac disease. If the tests are positive, other tests will be ordered to support the findings. This may include non-invasive procedures like capsule endoscopy or radiographic tests such as fluoroscopy or CT scans. Of the various approaches, only an intestinal biopsy (in which a tissue sample is taken directly from the small bowel) can provide definitive evidence of the disease.

Obtaining a celiac disease diagnosis can be a long process and, in most cases, will start with celiac blood tests.

Aims of Celiac Blood Testing

Antibody-based tests are used to diagnose a wide variety of diseases. They detect specific antibodies produced by the immune system that are uniquely structured to bind to the specific threat.

The accuracy of these tests can often vary considerably, in part because many antibodies are similar in structure and/or occur with multiple related diseases. This can affect the sensitivity of a test (the ability to produce a correct positive result) as well as the specificity of a test (the ability to produce a correct negative result).

This is the reason why antibody tests for celiac disease cannot be used on their own. Because there is a potential for false-positives and false-negatives, confirmatory tests are needed. Even newer tests with greater than 90% sensitivity and specificity are prone to user error and other factors that can undermine the accuracy of the test.

To ensure an accurate reading, you need to be eating gluten at the time of testing so that there are ample antibodies to detect. If you are not, you may end up with a false-negative reading despite having celiac disease.

Types of Antibody Test

There are a number of different antibody-based blood tests used to screen for celiac disease. The choice of test can differ for adults and children. Some are performed together as part of the initial screening process. Others may be ordered if the initial tests are negative or inconclusive but the symptoms are strongly suggestive of celiac disease.

Of the five types of immunoglobulins produced by the immune system—IgA, IgD, IgE, IgG, and IgM—immunoglobulin A is the type that predominates in celiac disease. For this reason, IgA tests are the most sensitive.

People who are IgA-deficient (common with autoimmune disorders such as type 1 diabetes, lupus, Hashimoto's thyroiditis, or rheumatoid arthritis) can undergo IgG testing instead. Because celiac disease is also autoimmune, IgA deficiency occurs at a rate that is 10 to 15 times greater than that of the general population.

The screening of celiac disease in adults and most children typically starts with the tissue transglutaminase (tTG) test. For children two and under, the deamidated gliadin peptide (DGP) test should also be used. Other antibody tests may be ordered for specific situations.

Tissue Transglutaminase (tTG) Test

Tissue transglutaminase (tTG) is an enzyme found in various tissues of the body, including the heart, liver, and small intestine. It plays a role in a number of biological functions, including wound healing, cell-to-cell adhesion, and the regulation of cell survival and death. It is also involved in the breakdown of certain proteins in gluten called gliadins.

The interaction between tTG and gliadins is complex. As tTG breaks down gluten into its constituent parts (gliadin and glutenin), the subsequent breakdown of gliadins in the bloodstream will further activate tTG in the small intestine, causing enzyme levels to spiral out of control.

The immune system will respond to this abnormal occurrence by producing defensive tTG antibodies that the tTG test can detect with a relatively high degree of accuracy.

The tTG test, also known as the anti-tissue transglutaminase test or anti-tTG, is considered the first-line option for antibody testing with a sensitivity of 93% and a specificity of 96.5%.

Because IgA antibodies typically predominate in celiac disease, testing for tTG IgA antibodies is preferred. If IgA deficiency is suspected, the IgG version may be used.

Deamidated Gliadin Peptide (DGP) Test

Gliadins are a component of gluten that is essential to giving bread its rise during baking. They are a class of water-soluble proteins the are easily absorbed by the intestines and are able to provoke an autoimmune response.

Deamidated gliadin is produced when acids or enzymes, most specifically tTG, break down gliadin in the digestive tract. In people with celiac disease, this response is amplified and provides a key marker for the disease.

The deamidated gliadin peptide (DGP) test is able to detect deamidated gliadin IgA with a specificity of 94% but a less-than-ideal sensitivity of 74%. Because of this, it is more often used in tandem with the tTG test to provide early evidence of celiac disease.

This is especially true in children two under who have not yet developed a robust immune response. For these children, the tTG test should be supported by a version of the DGP test that is able to detect IgA and IgG antibodies (sensitivity 75%, specificity 94%).

The DGP test has largely replaced the older antigliadin antibody (AGA) test, the latter of which detects antibodies for gliadin rather than antibodies produced when gliadin is broken down. When compared to the DGP and tTG tests, the AGA has a sensitivity of as low as 60.9%.

Endomysial Antibody (EMA) Test

The endomysial antibody (EMA) test boasts an even higher specificity than either the TTG or DGP tests (over 99%) as well as a sensitivity of around 93%. Despite its high degree of accuracy, the EMA test is very expensive and requires either a primate esophagus or human umbilical cord to complete the test.

Endomysial antibodies are produced in a layer of tissue surrounding muscles called the endomysium. The endomysium contains a form of tTG that, when exposed to gluten, will activate and churn out antibodies in an autoimmune response.

The EMA test is primarily used to detect IgA antibodies, although an IgG version is also available. Because the antibodies bind with smooth muscles, frozen esophagal or umbilical cord tissue is needed to draw the antibodies from the blood sample in high enough concentrations to elicit an accurate result.

The EMA test is most often used in people with classic celiac disease symptoms who have tested negative on less costly tTG and DGP tests.

Total Serum IgA

The total serum IgA test is used to check for IgA deficiency, the condition of which can cause a false-negative tTG-IgA or EMA reading. It is often used when a person tests negative for one or both of these tests. At other times, it is performed alongside the tTG to establish whether there is some degree of IgA deficiency that might otherwise influence the results.

If the total serum IgA test determines that you are IgA deficient, your doctor can order either a DGP-IgG test or a TTG-IgG test.

Celiac Disease Doctor Discussion Guide

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Other Blood Tests

There are other non-antibody-based blood tests that can be used in the screening process, generally before an intestinal biopsy is considered.

I-FABP Test

The intestinal fatty acid-binding protein (I-FABP) test detects a protein that is released into the blood whenever the intestines incur damage. Celiac disease is characterized by damage to the lining of the small intestine that over time reduces the body's ability to absorb nutrients.

Elevations of I-FAGP in blood can help evidence celiac disease even if antibody tests are inconclusive. Urine samples can also be tested for I-FABP.

Celiac Genetic Testing

Celiac genetic testing, also known as HLA typing, can also be used in the course of screening to rule out celiac disease as a cause. The test is able to detect gene complexes called human leukocyte antigens (HLA) that may predispose you to celiac disease, namely HLA-DQ2 and HLA-DQ8.

A positive genetic test result does not mean that you have celiac disease—since 55% of the general population have HLA-DQ2 and HLA-DQ8 compared to 98% of the celiac population—but it can exclude celiac disease as a cause if neither of the antigens are detected.

How the Tests Are Performed

For the antibody-based tests to be accurate, you will need to be on a gluten-containing diet until the test is performed. The same does not apply to the I-FABG or celiac genetic tests which do not require gluten to trigger an autoimmune response.

The tests are done in the same way as any blood draw:

  1. The skin on the arm or hand is cleaned with an antiseptic swab.
  2. An elastic band (tourniquet) is placed on the arm to get the veins to swell.
  3. A needle is inserted into a vein, usually in the crook of the elbow or the back of the hand.
  4. A blood sample is drawn into one or more vacuum-sealed test tubes (vacutainers).
  5. The needle and tourniquet are removed.
  6. The puncture site is bandaged.

Mild, short-term pain and redness may occur at the puncture site. Swelling and infection are uncommon but can occur. Call a doctor if you develop fever or if pain, swelling, or redness persists or worsens.

Celiac blood test results are usually returned within one to three days. EMA and celiac genetic test results may take longer.

A Word From Verywell

If the antibody tests are positive, your doctor will likely recommend that you undergo an endoscopy to directly view the lining of the small intestine.

During an endoscopy, the gastroenterologist will insert a tube through your stomach and into the top of the small intestine to obtain a sample of tissue to examine under the microscope. If the sample shows evidence of villous atrophy (the flattening of the finger-like lining of the intestine), celiac disease can be definitively diagnosed.

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