What is the initial diagnostic approach for patients suspected of having celiac disease, particularly regarding celiac serologies such as tissue transglutaminase antibody (tTGA) and endomysial antibody (EMA) tests?

From the Guidelines

The initial diagnostic approach for patients suspected of having celiac disease involves serological testing while the patient is on a gluten-containing diet, with tissue transglutaminase antibody (tTGA) IgA being the preferred first-line test due to its high sensitivity and specificity, as supported by the most recent study 1.

Key Considerations

• The patient should continue consuming gluten (equivalent to at least 4 slices of bread daily) for 6-8 weeks before testing, as a gluten-free diet can normalize antibody levels and heal intestinal mucosa, potentially leading to false-negative results 1.
• Total serum IgA measurement should be performed to rule out IgA deficiency, which occurs in about 2-3% of celiac patients and can cause false-negative results 1.
• If IgA deficiency is present, IgG-based tests (tTG-IgG or deamidated gliadin peptide antibodies) should be ordered instead 1.
• Endomysial antibody (EMA) testing is highly specific but more expensive and operator-dependent, so it's typically used as a confirmatory test when tTGA results are equivocal 1.

Diagnostic Approach

• Positive serological tests should be followed by an upper endoscopy with multiple duodenal biopsies to confirm the diagnosis histologically 1.
• Genetic testing for HLA-DQ2 and DQ8 haplotypes can be helpful in certain situations but is not routinely recommended as an initial diagnostic test 1.

Important Notes

• The diagnosis of celiac disease should be based on a combination of serological tests and intestinal biopsy, as recommended by the British Society of Gastroenterology 1.
• The American College of Gastroenterology (ACG) also recommends that all diagnostic serologic testing for celiac disease should be performed before a gluten-free diet is initiated 1.

From the Research

Celiac Serologies

• Celiac disease is associated with endomysial antibodies (EmA), which have recently been reported to be directed to tissue transglutaminase (tTG) 2
• The diagnosis of celiac disease often relies on the anti-tissue transglutaminase (tTG) antibody test, which has a sensitivity of 70.6% and specificity of 65.0% in clinical practice 3
• The endomysial antibody and the tissue transglutaminase antibody tests have very high sensitivities (93% for both) and specificities (>99% and >98% respectively) for the diagnosis of typical celiac disease with villous atrophy 4

Diagnostic Approach

• Serologic tests for antibodies against endomysium, transglutaminase, and gliadin identify most patients with celiac disease 5
• The human recombinant tissue transglutaminase antibody is the preferred test for screening asymptomatic people and for excluding celiac disease in symptomatic individuals with a low pretest probability (<25%) for celiac disease 4
• If the pretest probability is >25%, biopsy is preferred as the post-test probability of celiac disease with a negative test is still >2% 4

Test Characteristics

• The sensitivity of the anti-tTG antibody test is significantly lower in patients with partial villous atrophy (42.3%) compared to those with total villous atrophy (90.0%) 3
• There is significant variability in test characteristics among major commercial laboratories in the United States, with sensitivity ranging from 40.0% to 86.4% and specificity ranging from 41.7% to 100.0% 3
• The ELISA test for tTG correlates well with the traditional AGA and EmA tests and could be used as a new test for celiac disease, with high specificity and sensitivity compared to classical EmA and AGA tests 6