What are the laboratory tests for celiac disease (CD)?

From the Guidelines

Laboratory tests for celiac disease should begin with serological screening, including tissue transglutaminase antibodies (tTG-IgA) and total IgA levels, as recommended by the most recent guidelines 1. The tTG-IgA test is highly sensitive and specific for celiac disease, while total IgA measurement helps identify IgA deficiency, which could lead to false-negative results. If IgA deficiency is present, deamidated gliadin peptide antibodies (DGP-IgG) or tTG-IgG should be ordered instead, as suggested by the 2021 AGA clinical practice update 1. Endomysial antibody (EMA-IgA) testing may be used as a confirmatory test due to its high specificity, as noted in the 2006 AGA institute medical position statement 1. Genetic testing for HLA-DQ2 and HLA-DQ8 can be helpful to rule out celiac disease, as their absence makes the diagnosis unlikely, according to the 2019 AGA clinical practice update 1. A definitive diagnosis typically requires an intestinal biopsy showing characteristic villous atrophy, which should be performed while the patient is still consuming gluten, as recommended by the 2019 AGA clinical practice update 1 and the 2014 ACG guideline 1. Additional laboratory tests may include:

• Complete blood count to check for anemia
• Liver function tests
• Nutritional assessments for deficiencies in iron, folate, vitamin B12, and vitamin D, which are common in celiac disease due to malabsorption, as noted in the example answer. It is essential to perform all diagnostic serologic testing for celiac disease before initiating a gluten-free diet, as stated in the 2014 ACG guideline 1.

From the Research

Labs for Celiac Disease

• The following labs are used to diagnose celiac disease:
  • Tissue transglutaminase (tTG) antibody test 2, 3, 4, 5, 6
  • Endomysial antibody (EMA) test 2, 3, 5, 6
  • Deamidated gliadin peptide (DGP) antibody test 3, 4, 5, 6
  • Gliadin antibody test 2, 3, 6
• The sensitivity and specificity of these tests vary:
  • tTG antibody test: sensitivity 90.9% 2, 91% 3, 91.2% 5; specificity 90.9% 2, 98% 3, 87.5% 5
  • EMA test: sensitivity 80% 3, 85.7% 2; specificity 98.6% 2, 98% 3
  • DGP antibody test: sensitivity 91% 3, 94.4% 5, 92.7% 5; specificity 98% 3, 85.2% 5

Diagnostic Approach

• A 2-step approach using tTG first and then EMA can be used for diagnosis, with a sensitivity of 85.7% and specificity of 98.6% 2
• The use of DGP antibody test in combination with tTG test can offer the best sensitivity without loss of specificity in the diagnosis of celiac disease 3, 5
• Measurement of serum anti-tTG and DGP can identify patients with celiac disease with high sensitivity and specificity 5

Limitations

• A normal tTG level does not predict recovery of villous atrophy in patients with celiac disease on a gluten-free diet 2
• The conventional gliadin antibody test shows poor sensitivity and specificity 3