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

From the Guidelines

To test for celiac disease, the most reliable approach is a two-step process: blood tests followed by an intestinal biopsy if blood tests are positive, as recommended by the most recent guidelines 1. The initial blood test should be the tissue transglutaminase antibody test (tTG-IgA), which is highly sensitive and specific for celiac disease, with a sensitivity of 93% and specificity of 98% 1. It's essential to continue eating gluten before testing, as eliminating gluten can lead to false negative results. For accurate results, you should consume gluten daily for at least 6-8 weeks before testing. If the tTG-IgA test is positive, an endoscopic biopsy of the small intestine is typically performed to confirm the diagnosis by examining intestinal damage. Some doctors may also order additional blood tests like deamidated gliadin peptide antibodies (DGP IgA and IgG) or endomysial antibodies (EMA) 1. For individuals with IgA deficiency, which affects about 2-3% of celiac patients, specific IgG-based tests are recommended 1. Genetic testing for HLA-DQ2 and HLA-DQ8 can be useful to rule out celiac disease but cannot confirm it, as nearly 100% of individuals diagnosed with celiac disease exhibit this specific genetic profile 1. These comprehensive tests are necessary because celiac disease is an autoimmune condition where gluten triggers an immune response that damages the small intestine, leading to various symptoms and potential complications if left undiagnosed. Key points to consider in the diagnosis of celiac disease include:

• The importance of serology in diagnosis, with tTG-IgA being the first-line screening test 1
• The need for intestinal biopsy to confirm the diagnosis, with evaluation of villous to crypt cell ratio in well-oriented biopsy specimens being crucial 1
• The role of HLA typing in ruling out celiac disease, particularly in cases with uncertain diagnosis 1
• The consideration of IgA deficiency and the use of IgG-based tests in such cases 1

From the Research

Celiac Disease Testing

• Celiac disease is an immune-mediated disorder that affects individuals who are exposed to gluten-containing grains, and it can be diagnosed through various tests 2.
• The recommended initial screening for celiac disease is immunoglobulin A tissue transglutaminase serologic testing, which can be used for all age groups 2.
• Esophagogastroduodenoscopy with small bowel biopsy is recommended to confirm the diagnosis in most patients, including those with a negative serologic test for whom clinical suspicion of celiac disease persists 2.

Types of Tests

• Immunoglobulin A tissue transglutaminase (tTG) serologic testing is a common test used to screen for celiac disease, with a sensitivity of approximately 95% 3.
• Endomysial antibody (EMA) testing is another test used to diagnose celiac disease, with a high specificity of 100% 3, 4.
• Genetic testing for human leukocyte antigen alleles DQ2 or DQ8 may be performed in select cases to diagnose celiac disease 2.

Test Limitations

• Tests for serum tTG IgA and EMA IgA levels have low sensitivity (below 50%) in detecting persistent villous atrophy in patients with celiac disease who are following a gluten-free diet 5.
• Positive tTG antibodies with negative EMA antibodies have a low rate of celiac disease, and confirmation with EMA is advised when tTG is performed as a first-level screening for suspected celiac disease 6.
• There is a high variability of values between laboratories when using commercial kits for quantitative determination of antitissue transglutaminase, which can affect the accuracy of test results 4.

Diagnostic Criteria

• A gluten-free diet for life is the primary treatment for celiac disease, and patients may benefit from support groups and education on common and hidden sources of gluten 2.
• Patients with celiac disease who do not respond to a gluten-free diet should have the accuracy of the diagnosis confirmed, have their diet reassessed, and be evaluated for coexisting conditions 2.
• Biopsies may be avoided in children with high immunoglobulin A tissue transglutaminase and a positive test for immunoglobulin A endomysial antibodies in a second serum sample 2.