Blood Test for Celiac Disease
The IgA tissue transglutaminase antibody (tTG-IgA) is the recommended first-line blood test for diagnosing celiac disease, and it must be performed while the patient is consuming a gluten-containing diet. 1, 2
Initial Serologic Testing Algorithm
Order tTG-IgA plus total IgA level simultaneously as your initial diagnostic workup. 2, 3 This combination is critical because:
- tTG-IgA has sensitivity of 90-96% and specificity >95%, making it the most efficient single serologic test 1, 2
- Total IgA measurement identifies IgA deficiency (occurs in 1-3% of celiac patients), which causes false-negative tTG-IgA results 2, 3
- The patient must be consuming at least 10g of gluten daily for 6-8 weeks before testing, as gluten-free diet causes false-negative results 2, 3
Confirmatory Serologic Testing
If tTG-IgA is elevated (especially >10× upper limit of normal), order IgA endomysial antibody (EMA-IgA) as confirmatory testing. 2, 3
- EMA-IgA has excellent specificity of 99.6%, though it is more time-consuming and operator-dependent than tTG-IgA 1
- The combination of tTG-IgA >10× upper limit of normal plus positive EMA-IgA approaches 100% positive predictive value for celiac disease 3
Special Population Considerations
In IgA-deficient patients, switch to IgG-based testing: order IgG tissue transglutaminase (tTG-IgG) and/or IgG deamidated gliadin peptide (DGP-IgG). 1, 2 Note that IgG-based tests are markedly less sensitive and specific than IgA-based tests in patients with normal IgA levels. 1
In children under 2 years of age, combine tTG-IgA with IgG and IgA deamidated gliadin peptides for improved sensitivity. 1, 2, 3
Tests That Are NOT Recommended
Do not order IgA or IgG antigliadin antibodies (AGA) for primary detection—their diagnostic performance is inferior to tTG-IgA and EMA-IgA. 1 The older gliadin antibody tests have been supplanted by the more accurate tTG-IgA test. 1
Combining multiple serologic tests instead of tTG-IgA alone may marginally increase sensitivity but reduces specificity and is not recommended in low-risk populations. 1
Critical Requirement: Biopsy Confirmation
Positive serology alone is insufficient for diagnosis in adults—upper endoscopy with multiple duodenal biopsies remains mandatory. 1, 2 The biopsy protocol requires:
- At least 6 biopsy specimens total: 1-2 from the duodenal bulb and at least 4 from the second part of the duodenum or beyond 1, 3
- Characteristic histologic findings include villous atrophy, crypt lengthening, and increased intraepithelial lymphocytes 1, 2
- Lymphocytic infiltration without villous atrophy is NOT specific for celiac disease and requires consideration of other causes (H. pylori infection, bacterial overgrowth, autoimmune disorders) 1
When to Consider HLA-DQ2/DQ8 Genetic Testing
HLA-DQ2 and HLA-DQ8 testing has >99% negative predictive value (absence of both alleles essentially rules out celiac disease) but should NOT be used routinely. 1, 2, 3 Order genetic testing only in these specific scenarios:
- Celiac disease strongly suspected despite negative serology 1, 4
- Equivocal small-bowel histologic findings 1, 2
- Patient already on gluten-free diet without prior diagnostic testing 1, 2
- Discrepant celiac-specific serology and histology 1, 2
Note that 25-30% of the white population carries HLA-DQ2, so positive genetic testing alone cannot diagnose celiac disease. 1
Common Pitfalls to Avoid
Never initiate a gluten-free diet before completing diagnostic testing—this is the most common error that leads to false-negative results and diagnostic uncertainty. 1, 2, 3
Do not diagnose celiac disease based on symptom improvement with gluten-free diet alone—this has very low positive predictive value and should not be used without supportive serologic and histologic evidence. 1, 2
Do not rely solely on serology without biopsy confirmation in adults—this leads to misdiagnosis. 1, 2 The exception is children with tTG-IgA ≥10× upper limit of normal, positive EMA-IgA, and positive HLA-DQ2/DQ8, where biopsy may be avoided per pediatric guidelines. 2, 4