What are all the potential blood tests for celiac disease?

Blood Tests for Celiac Disease

The primary blood tests for celiac disease include IgA tissue transglutaminase antibody (tTG-IgA) with total IgA level, IgA endomysial antibody (EMA-IgA), IgG-based tests for IgA-deficient patients, and HLA-DQ2/DQ8 genetic testing in select cases. 1, 2

Primary Serologic Tests

First-Line Screening

• IgA tissue transglutaminase antibody (tTG-IgA) is the preferred initial screening test with sensitivity of 90.7% and specificity of 87.4% in adults at 15 U/mL threshold, and sensitivity of 97.7% with specificity of 70.2% in children at 20 U/mL threshold 1, 2, 3
• Total IgA level must be measured simultaneously with tTG-IgA to identify IgA deficiency, which occurs in 1-3% of celiac patients and causes falsely negative IgA-based tests 1, 2, 3

Confirmatory Serologic Tests

• IgA endomysial antibody (EMA-IgA) serves as a second-line confirmatory test with excellent specificity of 99.6% in adults and 93.8% in children 1, 2, 4
• When tTG-IgA exceeds 10 times the upper limit of normal and EMA-IgA is positive in a second blood sample, the positive predictive value approaches 100% 1, 2

Tests for IgA-Deficient Patients

• IgG deamidated gliadin peptide (DGP-IgG) is the preferred IgG-based test in IgA-deficient patients, with superior diagnostic accuracy showing 93.6% sensitivity and 99.4% specificity in adults 1, 2
• IgG tissue transglutaminase (tTG-IgG) can be used in IgA deficiency but has limited utility with sensitivity ranging only 40.6-84.6% and specificity 78.0-89.0%, making it less reliable than DGP-IgG 1
• IgG endomysial antibody (EMA-IgG) is highly effective in IgA-deficient patients, with all IgA-deficient celiac patients testing positive in research studies 1

Important caveat: IgG-based testing should not be used as primary screening when total IgA is normal, as it lacks specificity and generates frequent false-positive results in that setting 1

Genetic Testing

• HLA-DQ2 and HLA-DQ8 testing has limited diagnostic value but provides >99% negative predictive value—absence of both alleles essentially rules out celiac disease 1, 2, 4, 5
• HLA testing is reserved for specific scenarios: patients with equivocal histology, discordant serology, those already on a gluten-free diet without prior testing, or when celiac disease is strongly suspected despite negative serology 1, 2, 4

Pediatric-Specific Testing

• In children under 2 years of age, tTG-IgA should be combined with IgG and IgA deamidated gliadin peptides for improved sensitivity 2, 4

Monitoring Tests (Post-Diagnosis)

• Complete blood count (CBC) to assess for anemia and nutritional status 1
• Iron studies (serum iron, ferritin, transferrin saturation) to evaluate iron deficiency 1
• Folate and vitamin B12 levels to assess for malabsorption 1
• Other micronutrients including calcium, vitamin D, zinc, and fat-soluble vitamins to evaluate nutritional status 1
• Liver function tests to monitor for hepatic involvement 1

Tests NOT Recommended

• Non-deamidated IgA/IgG gliadin antibody assays (older-generation tests) provide no additional diagnostic benefit and should be omitted 6
• Salivary antibody testing lacks sufficient accuracy and is not advised 6
• D-xylose testing should not be used in evaluation 6
• Intestinal permeability testing is not recommended as a diagnostic tool 6
• Small-bowel follow-through imaging does not add diagnostic value 6

Critical Testing Requirements

• All serologic testing must be performed while the patient is consuming at least 10g of gluten daily for 6-8 weeks to avoid false-negative results 1, 2, 4
• If a patient has already started a gluten-free diet, they should resume normal gluten intake (e.g., three slices of wheat bread daily) for 1-3 months before repeat testing 1

Common Pitfalls

• Never initiate a gluten-free diet before completing diagnostic testing, as this invalidates both serologic and histologic assessments 1, 6, 2
• Do not diagnose celiac disease based solely on serology without biopsy confirmation in adults 1, 2
• Avoid ordering multiple antibody panels simultaneously in low-risk individuals, as this reduces specificity without meaningful increase in sensitivity 6
• Different tTG-IgA assays have varying sensitivity for detecting suboptimal treatment response, so use the same assay for serial monitoring 1