Recommended Lab Test for Celiac Disease
The IgA tissue transglutaminase antibody (tTG-IgA) is the recommended first-line screening test for celiac disease, with total IgA levels measured simultaneously to rule out IgA deficiency. 1, 2, 3
Initial Serologic Testing Approach
Order IgA tTG as the primary screening test with sensitivity of 90-96% and specificity >95% in adults, and even higher sensitivity (97.7%) in children at standard thresholds 1, 2, 3
Measure total IgA levels concurrently to identify IgA deficiency, which occurs in 1-3% of celiac disease patients and would cause falsely negative IgA-based test results 1, 2, 4, 3
Testing must be performed while the patient is consuming gluten (at least 10g daily for 6-8 weeks) because positive serologic results resolve and histologic findings improve with gluten removal 1, 2, 3
Confirmatory Testing Based on Initial Results
If tTG-IgA is >10× upper limit of normal, add IgA endomysial antibody (EMA-IgA) as a confirmatory test with excellent specificity of 99.6% 1, 2, 3
If IgA deficiency is detected, switch to IgG-based tests including IgG deamidated gliadin peptide (DGP-IgG) or IgG tTG, which have excellent sensitivity and specificity in this population 1, 3
If tTG-IgA is negative but clinical suspicion remains high, measure serum IgA level to exclude IgA deficiency, or consider HLA-DQ2/DQ8 testing which has >99% negative predictive value 1, 2, 3
Tests to Avoid
Do not use IgA or IgG antigliadin antibodies as the primary screening test, as their diagnostic performance is inferior to tTG-IgA and EMA 1
Do not use IgG tTG in patients with normal IgA levels, as IgG-based tests are markedly less sensitive and specific than IgA-based tests in IgA-sufficient individuals 1, 4
Routine measurement of serum IgA levels alongside tTG-IgA is not warranted as a first step unless IgA deficiency is strongly suspected based on clinical history 1
Special Population Considerations
In children under 2 years of age, combine tTG-IgA testing with IgG and IgA deamidated gliadin peptides for improved sensitivity 3
In patients already on a gluten-free diet, they must resume a normal diet with three slices of wheat bread daily for 1-3 months before repeat testing to avoid false-negative results 2
Critical Pitfalls to Avoid
Never initiate a gluten-free diet before completing diagnostic testing, as this leads to false-negative serology and inconclusive biopsy results with high strength of evidence 2, 4, 3
Do not rely solely on serology without biopsy confirmation in adults, as intestinal biopsy remains the gold standard for diagnosis despite high serologic accuracy 1, 2, 3
Recognize that seronegative celiac disease can occur, requiring biopsy for diagnosis when clinical suspicion is high despite negative serology 2
Different tTG-IgA assays have varying sensitivity, so interpret results in the context of the specific assay's reference range and performance characteristics 4