The Perfect Blend of East and West




How to accurately test for Celiac disease using Antibody testing

by Marion Bachra, MS, RD, a Bozeman Nutritionist and a Bozeman Chinese Herbalist

published in the May 2006 Montana Gluten-Free Friends’ Society Newsletter

Antibody testing to help identify those with Celiac disease is accurate after the age of two. Antibody testing can only be done if the person being tested is currently eating gluten containing foods. Some health care practitioners will test for antibodies even though the client stopped consuming gluten several months or even years previously with the consequence that the client with Celiac disease has a false negative test result. A false negative test result is a negative test result even though the person tested has Celiac disease. A false positive test result is a positive test result even though the person tested does not have Celiac disease. For instance, a false positive test result can occur when only anti-gliadin antibodies are used to identify Celiac disease. Several other potential testing errors can also occur. Ideally, a diagnostic test needs to have a high degree of sensitivity and specificity. Sensitivity is the ability of the test to identify those with Celiac disease as having the disease, while Specificity is the ability of the test to identify those without Celiac disease as not having the disease. The problem with testing for Celiac disease lies in the fact that when the practitioner uses tests that solely rely on Immunoglobin A antibody production, but fails to check whether or not the person has the ability to produce enough Immunoglobin A antibodies, a false negative test for Celiac disease can result. People with Celiac disease have a 10 to 15 fold increase in Immunoglobin A deficiency which means that they are unable to produce enough Immunoglobin A to obtain a true positive test result. What that means is that when the practitioner does not rule out Immunoglobin A deficiency and only uses Immunoglobin A antibody dependent tests, a person with Celiac disease and Immunoglobin A Deficiency will test negative for Celiac disease and be told that they do not have Celiac disease. Let’s take a closer look at the most commonly used type of Celiac antibody testing methods and how to test for Immunoglobin A deficiency.

Total Immunoglobin A Antibodies (Total IgA)

This test is not a diagnostic test for Celiac disease, but this test needs to be done to rule out Immunoglobin A deficiency when using Immunoglobin A dependent testing. Without this information, Immunoglobin A antibody dependent Celiac tests can produce false negative test results in a person with Celiac disease who is also Immunoglobin A deficient. Total IgA production increases with age, therefore the test results are age-adjusted. Total IgA production needs to be checked when using the two most commonly used Celiac tests, namely Immunoglobin A Anti-tissue Transglutaminase (IgA-tTG) and Immunoglobin A Anti-endomysial Antibody (IgA EMA) tests.

IgG Anti-tissue Transglutaminase (IgG-tTG) & IgA Anti-tissue Transglutaminase (IgA-tTG)

Tissue Transglutaminases are enzymes which are located in the intestinal submucosa and are used to repair collagen and connective tissue after tissue injury. After ruling out Immunoglobin A deficiency, IgA-tTG testing has a 98.2% sensitivity and a 94.3% specificity for identifying Celiac disease. IgG-tTG testing has a 84.6% sensitivity and a 100% specificity for identifying Celiac disease. Sensitivity is the ability of the test to identify those with Celiac disease as having the disease, while Specificity is the ability of the test to identify those without Celiac disease as not having the disease. Negative test results for both IgA-tTG and IgG-tTG identifies in a IgA competent individual rules out Celiac disease with a 100% specificity. A positive IgA-tTG or IgG-tTG test result, but negative IgG and IgA anti-gliadin antibody results rules out Celiac disease with a 95% specificity, because about 5% of those with Celiac disease don’t produce anti-gliadin antibodies. However, this type of test result can also be due other inflammatory or autoimmune diseases and further testing might be warranted.

IgA Anti-endomysial Antibodies (IgA-EMA)

This antibody test relies on sufficient Immunoglobin A production. A person with Celiac disease and Immunoglobin A deficiency will always get a false negative test result. Some practitioners will only order this test without checking for sufficient Immunoglobin A production. Only people who have Celiac disease and who produce enough Immunoglobin A can test positive for IgA-EMA. One of the two labs that I work with, Genova Diagnostics, formerly named Great Smokies Diagnostics, only test for IgA-EMA when the person produces sufficient Immunoglobin A and has elevated Anti-tissue Transglutaminase IgA antibodies. IgA-EMA has a 97% sensitivity and a 98% specificity for identifying Celiac disease in people with sufficient Immunoglobin A production. The endomysium is the connective tissue that lines smooth muscles bundles. Circulating levels of anti-endomysal antibodies are highly prevalent in people with Celiac disease. What makes this test unique is that it can help identify Latent Celiac disease or people with asymptomatic Celiac disease and a normal intestinal biopsy, but who are at high risk for developing overt Celiac disease. IgA-EMA have been shown to elevate before small intestinal histological changes take place.

IgA Anti-gliadin antibodies (IgA-AGA) & IgG Anti-gliadin antibodies (IgG-AGA)

Anti-gliadin antibodies cannot be used by themselves to identify Celiac disease, since 5% to 12% of individuals without Celiac disease have an elevation in one or two of the anti-gliadin antibodies usually because of an inflammatory or other type of autoimmune disease. When Anti-gliadin antibody testing is used as the sole test to help identify Celiac disease, the probability of getting a false positive test result is high, namely, 48% when using only using IgA anti-gliadin antibodies, and 22% when only using IgG anti-gliadin antibodies. On the other hand, when both anti-gliadin antibodies are negative, but IgG and/or IgA Anti-tissue Transglutaminase are positive, Celiac disease is unlikely, and assessment for other possible autoimmune condition is necessary. When both IgA-AGA and IgG-AGA are negative, the specificity is 95% for ruling out Celiac disease, since about 5% of those with Celiac disease don’t produce anti-gliadin antibodies. A negative IgA-AGA in a IgA competent individual rules Celiac disease with a 95% specificity, while a negative IgG-AGA rules Celiac disease with a 93% specificity.

IgA Anti-gliadin antibodies (IgA-AGA)

IgA-AGA can help rule out Celiac disease with a 95% specificity in persons who are not Immunoglobin A deficient, but only has a 52% sensitivity for identifying Celiac disease, since people with inflammatory or other type of autoimmune disease can show an elevation in IgG-AGA even though they do not have Celiac disease. IgA-AGA is the best Antibody test to monitor adherence to a gluten free diet in a person who produces sufficient Immunoglobin A. IgA-AGA begin to decrease in 1 month after eating a gluten free diet and normalize in 1 year after eating a gluten free diet.

IgG Anti-gliadin antibodies (IgG-AGA)

IgG-AGA can help rule out Celiac disease with a 93 % specificity, and has a 88% sensitivity for identifying Celiac disease, since people with inflammatory or other type of autoimmune disease can show an elevation in IgA-AGA even though they do not have Celiac disease. IgG-AGA is the best Antibody to monitor adherence to a gluten free diet in a person who is Immunoglobin A deficient. IgG-AGA begin to decrease in 6 months after being on a gluten free diet and normalize in 2 years after eating a gluten free diet.

Conclusion

To accurately use Antibody testing to help identify or rule out Celiac disease, the person being tested must be eating gluten.  The health care practitioner should be ordering a combination panel of:

a. IgG & IgA anti-tissue transglutaminase

b. The person must be tested for Immunoglobin A deficiency.

c. Test for IgA endomysial antibodies if the person is not Immunoglobin A deficient.

d. The person must be tested for IgG & IgA anti-gliadin antibodies, if IgG or IgA anti-tissue transglutaminase or IgA endomysial antibodies are positive

Following these steps will avoid that a person with Celiac disease will get back a false negative test result and that a person without Celiac disease will get back a false positive test result.

Gliadin IgA antibodies begin to decrease in 1 month after eating a gluten free diet and normalize in 1 year after eating a gluten free diet.

Gliadin IgG antibodies begin to decrease in 6 months after being on a gluten free diet and normalize in 2 years after eating a gluten free diet.

Transglutaminase IgG antibodies are substantially reduced after 3 months and are further reduced after 6 months and normalize in 2 years after eating a gluten free diet.

Transglutaminase IgA antibodies are substantially reduced after 3 months and are further reduced after 6 months and normalize in 9 to 24 months after eating a gluten free diet.

Endomysial IgA antibodies are substantially reduced 3 months after eating a gluten free diet, and normalize in 12 to 18 months after eating a gluten free diet.