What labs are used to diagnose celiac disease?

Diagnostic Labs for Celiac Disease

The primary diagnostic test for celiac disease is IgA tissue transglutaminase antibody (tTG-IgA), which should be performed while the patient is on a gluten-containing diet, followed by intestinal biopsy for confirmation in adults. 1

Initial Serological Testing

• IgA tissue transglutaminase antibody (tTG-IgA) is the preferred first-line screening test with high sensitivity (90-96%) and specificity (>95%) 1, 2
• Total IgA levels should be measured simultaneously to rule out IgA deficiency, which could cause false-negative results 3, 1
• Testing must be performed while the patient is on a gluten-containing diet (at least 10g daily for 6-8 weeks) to avoid false-negative results 1, 2
• In patients with tTG-IgA levels >10x upper limit of normal, IgA endomysial antibody (EMA-IgA) should be performed as a confirmatory test with excellent specificity (99.6%) 1, 4

Testing in Special Populations

• In IgA-deficient patients, IgG-based tests should be used instead:
  • IgG deamidated gliadin peptide (DGP-IgG) 1, 4
  • IgG tissue transglutaminase (tTG-IgG) 1
• In children under 2 years of age, tTG-IgA testing should be combined with IgG and IgA deamidated gliadin peptides for improved sensitivity 3, 2
• Antibodies directed against native gliadin are no longer recommended for primary detection due to poor sensitivity and specificity 3, 5

Confirmatory Testing

• Upper endoscopy with small bowel biopsy remains the gold standard for diagnosis in adults 1, 2
• Multiple duodenal biopsies are required:
  • 1-2 samples from the duodenal bulb 3
  • At least 4 samples from the distal duodenum 3, 1
• Characteristic histologic findings include villous atrophy, crypt lengthening, and increased intraepithelial lymphocytes 1, 6

Genetic Testing

• HLA-DQ2 and HLA-DQ8 testing has high negative predictive value (>99%) and is useful in specific scenarios:
  • When celiac disease is strongly suspected despite negative serology 1, 2
  • In patients with equivocal small-bowel histologic findings 3
  • In patients already on a gluten-free diet without prior testing 3, 1
  • In patients with discrepant celiac-specific serology and histology 3

Biopsy-Avoidance Strategies

• In children with tTG-IgA ≥10× upper limit of normal, positive EMA-IgA, and positive HLA-DQ2/DQ8, biopsy may be avoided according to pediatric guidelines 1, 2
• During the COVID-19 pandemic, similar non-biopsy protocols were temporarily adopted for adults with high tTG-IgA levels 3

Common Pitfalls to Avoid

• Initiating a gluten-free diet before completing diagnostic testing can lead to false-negative results 1, 4
• Relying solely on serology without biopsy confirmation can lead to misdiagnosis in adults 1, 4
• Lymphocytic infiltration of the intestinal epithelium without villous atrophy is not specific for celiac disease and requires consideration of other causes 3
• Serological tests have poor sensitivity (<50%) for detecting persistent villous atrophy in patients already on a gluten-free diet 7
• Improvement of symptoms after starting a gluten-free diet has a low positive predictive value for celiac disease and should not be used for diagnosis without supportive evidence 3

Follow-up Testing

• Follow-up serology should be performed at 6 and 12 months after diagnosis, and yearly thereafter 1
• Negative serology after treatment does not guarantee intestinal mucosal healing 1, 7
• Persistently elevated antibodies usually indicate ongoing gluten exposure 1, 4