Serologic testing for celiac disease in patients with IgA deficiency

Expires: March 11, 2027



Photo of Julia Lehman, M.D. 800x800

Julia Lehman, M.D.
Professor of Dermatology and Laboratory Medicine and Pathology
Department of Dermatology
Mayo Clinic, Rochester, Minnesota



Today I’d like to talk about serologic testing for celiac disease in patients with IgA deficiency. 

My name is Dr. Julia Lehman, and I am the director of the Mayo Clinic Immunodermatology Laboratory at Mayo Clinic in Rochester, Minnesota.


I have no disclosures.

I’d like to thank Dr. Absah, pediatric gastroenterologist, who reviewed this presentation.

Celiac disease

Celiac disease is characterized by inflammation of the small bowel that is triggered by exposure to gluten in the diet. Celiac disease is usually mediated by IgA antibodies are directed against tissue transglutaminase.

Celiac disease can lead to a number of symptoms, including diarrhea and constipation, as well as malabsorption, weight loss, bloating, and abdominal discomfort.

In addition, patients can have signs of disease including iron deficiency anemia, vitamin B12 deficiency, recurrent aphthous stomatitis (or severe canker sores), or a pruritic blistering rash called dermatitis herpetiformis.

Failure to thrive or short stature may be the presenting signs in children. Adults may also develop premature osteoporosis, neuropathy, nonhereditary cerebellar ataxia, or autoimmune thyroid disease.

Testing for celiac disease

The approach to testing for celiac disease depends on the pretest probability of the patient and his/her likelihood of having celiac disease. 

In patients with low pretest probability for celiac disease, generally a serologic testing screen is undertaken.  This involves a tissue transglutaminase or an antiendomysial antibody test, both of which are IgA tests. If either test result is positive, then further diagnostic evaluation for adults involves upper endoscopy with small bowl biopsy.

If the patient has moderate to high probability based on genetic predisposing factors, or based on the presence of highly characteristic symptoms, then that patient would undergo a serologic screen with either tissue transglutaminase IgA antibodies or antiendomysial or antigliadin IgA antibodies, as well as a total IgA level. The purpose of the total IgA level is to make sure the patient isn’t IgA deficient. More about that in a minute. Also, these patients will often undergo HLA typing to assess their likelihood of having celiac disease. 

Reasons for false-negative serologic testing

False-negative testing can occur if the patient has already begun following a gluten-free diet or a low gluten diet. Testing may turn negative within just weeks of a strict diet. In addition, no test has perfect testing sensitivity, so false-negative results may occur due to technical limitations. In addition, patients with mild disease may have a negative test result. 

One of the most important reasons for a falsely negative test, and one we will highlight today with today’s “Hot Topic” presentation, is IgA deficiency.   

IgA deficiency

Patients with celiac disease are substantially more likely than the general population to have IgA deficiency. When a patient is known to have IgA deficiency, then IgG testing should be pursued. This testing approach can be achieved with the IgG deaminated gliadin peptide (DGP) test, the IgG tissue transglutaminase (tTG) antibody test, or the IgG antienodmysial antibody (EMA) test.

When is it helpful to order IgG serologic studies?

So, when is it helpful to order the IgG serologic studies for celiac disease? The most important reason to order these studies would be to optimize diagnostic sensitivity in patients suspected of having celiac disease but with negative IgA testing. In addition, it can be used to establish a diagnosis of celiac disease in a patient known to be IgA deficient.

When is IgG serologic testing less helpful?

When is IgG serologic testing less helpful? IgG serologic testing is less helpful when patients are known not to be IgA deficient, when they are asymptomatic, and when they otherwise have a low pretest probability of celiac disease. In addition, IgG serologic testing is not validated for monitoring adherence to a gluten-free diet. 


In summary, celiac disease is mediated by tissue transglutaminase antibodies, typically of the IgA isoform. However, patients with celiac disease are at higher risk of having IgA deficiency. In this setting, IgA-based testing for celiac disease is often negative, complicating the clinical picture. In that setting, we recommend IgG antibody testing, either against gliadin, tissue transglutaminase, or endomysium, to establish the diagnosis of celiac disease. 

Thank you very much for your attention.


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