What is the initial test for celiac disease (CD)?

From the Guidelines

The initial test for celiac disease should be a blood test measuring tissue transglutaminase antibodies (TG2Ab) and total IgA levels, as it has high sensitivity (93%) and specificity (98%) 1. This test should be performed while the patient is still consuming gluten, as eliminating gluten before testing can lead to false-negative results.

• Patients should continue their normal gluten-containing diet for at least 6-8 weeks prior to testing.
• If the TG2Ab test is positive, the next step is typically an endoscopic biopsy of the small intestine to confirm the diagnosis.
• For patients with IgA deficiency, alternative tests like deamidated gliadin peptide (DGP) antibodies or TG2Ab IgG may be used. Key points to consider:
• The diagnostic approach to detecting celiac disease has undergone important changes in recent years, with serologic tests becoming a relatively sensitive and specific way to initially detect the disease 1.
• The IgA antiendomysial antibody (EMA) and the IgA tTGA are both sensitive and specific for celiac disease, but the IgA tTGA is more convenient and has a slightly higher sensitivity 1.
• A systematic review with meta-analysis found that serological tests for coeliac disease are highly sensitive and specific in both adults and children, but the review highlighted the need for more robust and up-to-date evaluations of the accuracy of these tests 1. It's essential to complete the diagnostic process before starting a gluten-free diet, as dietary changes can interfere with accurate diagnosis. These blood tests detect antibodies that the body produces in response to gluten exposure when the autoimmune reaction characteristic of celiac disease is present.

From the Research

Initial Test for Celiac Disease

• The initial test for celiac disease is based on the detection of anti-transglutaminase (tTG) IgA antibodies 2, 3, 4.
• The tTG IgA antibody test is the preferred test for screening patients for celiac disease 4.
• Total serum IgA level should be measured to exclude selective IgA deficiency and to avoid false-negative test results 4.
• If the tTG IgA antibody test is positive, the patient should be referred to a gastroenterologist for endoscopic small intestinal biopsies to confirm the diagnosis 4.
• Testing for human leukocyte antigens DQ2 and DQ8 can help exclude the diagnosis of celiac disease 4.

Serological Tests

• Serological tests, such as anti-endomysium and tissue transglutaminase IgA antibodies, have proven to be sensitive and specific markers for the diagnosis and follow-up of patients on a gluten-free diet 5, 3.
• Assays testing for IgG antibodies are recommended upon IgA-deficiency 5.
• Modern serological assays can identify most untreated celiac disease patients and are also increasingly being used to establish a diagnosis 6.
• However, serological tests have several challenges, including a lack of standardization, variable sensitivity and specificity of commercial assays, and inadequate sensitivity for monitoring adherence to a gluten-free diet 6.

Interpretation of Test Results

• A positive tTG IgA antibody test result should be interpreted with caution, as it can be due to the lower specificity of the anti-tTG test or the lower sensitivity of the EMA test 2.
• The overall agreement among different anti-tTG methods can range from 28.5% to 77.7% 2.
• Patients with positive anti-tTG/negative EMA have a low probability of being affected by celiac disease 2.
• The laboratory report should comment on any discordant results, suggesting consideration of the data in the proper clinical context and referral to a celiac disease reference center for prolonged follow-up 2.