What labs are used to diagnose celiac disease?

Laboratory Testing for Celiac Disease

The primary laboratory test for diagnosing celiac disease is IgA tissue transglutaminase antibody (tTG-IgA) combined with total IgA level measurement, performed while the patient consumes a gluten-containing diet. 1, 2

Initial Serologic Testing

Order these labs first:

• IgA tissue transglutaminase antibody (tTG-IgA) - This is the single best screening test with sensitivity of 90-96% and specificity >95% 1, 2
• Total IgA level - Must be measured simultaneously to identify IgA deficiency, which occurs in 1-3% of celiac patients and causes false-negative tTG-IgA results 1, 2, 3

Critical requirement: The patient must be consuming at least 10g of gluten daily for 6-8 weeks before testing, as avoiding gluten causes false-negative results 2, 4, 3

Confirmatory Serologic Testing

When tTG-IgA is elevated (especially >10× upper limit of normal):

• IgA endomysial antibody (EMA-IgA) - Perform this as confirmatory testing with excellent specificity of 99.6% 1, 2
• When tTG-IgA is >10× upper limit of normal AND EMA-IgA is positive, the positive predictive value for celiac disease approaches 100% 1, 4

Testing for IgA-Deficient Patients

If total IgA is low or absent, order these IgG-based tests instead:

• IgG tissue transglutaminase (tTG-IgG) 1, 2, 3
• IgG deamidated gliadin peptide (DGP-IgG) 2, 3

Important caveat: IgG isotype testing for tTG antibody is NOT specific in patients with normal IgA levels and should not be used in that setting 1, 4, 3

Genetic Testing (Limited Role)

HLA-DQ2 and HLA-DQ8 testing:

• Has >99% negative predictive value - absence of both alleles essentially rules out celiac disease 2, 4, 3
• Order this test when celiac disease is strongly suspected despite negative serology, in patients with equivocal biopsy findings, or in patients already on a gluten-free diet who were never properly tested 1, 2
• Do NOT order HLA testing when tTG-IgA is highly elevated, as it adds no diagnostic value in this scenario 4

Special Population Considerations

In children under 2 years:

• Combine tTG-IgA with IgG and IgA deamidated gliadin peptides for improved sensitivity 2, 4, 3

Tests to Avoid

Do NOT order these tests:

• Non-deamidated IgA/IgG gliadin antibodies - These confer no additional diagnostic benefit for adult celiac disease 5
• IgG-based tests in patients with normal IgA levels - These are markedly less accurate and should not be used 2

Follow-Up Serologic Testing

After diagnosis and initiation of gluten-free diet:

• Repeat tTG-IgA at 6 months, 12 months, then yearly thereafter 1, 2
• Persistently positive serology usually indicates ongoing gluten exposure and intestinal damage 1, 2, 3
• Critical pitfall: Negative serology does NOT guarantee intestinal mucosal healing - patients with persistent symptoms require repeat endoscopic biopsies even with negative antibodies 1, 2

Common Diagnostic Pitfalls

• Never start a gluten-free diet before completing diagnostic testing - this leads to false-negative results and may require 1-3 months of gluten rechallenge (three slices of wheat bread daily) before accurate retesting 1, 3
• Do not rely solely on serology - intestinal biopsy remains the gold standard for diagnosis in adults, even with highly elevated antibodies 2, 4, 3
• Seronegative celiac disease can occur and requires biopsy for diagnosis 2