What are the recommended lab tests for diagnosing celiac disease?

Recommended Laboratory Tests for Diagnosing Celiac Disease

The most efficient initial test for diagnosing celiac disease is the IgA tissue transglutaminase antibody (tTG-IgA) test, which should be performed while the patient is on a gluten-containing diet. 1

Diagnostic Algorithm for Celiac Disease

Step 1: Initial Serologic Testing

• Primary test: IgA tissue transglutaminase antibody (tTG-IgA)
  • Sensitivity: 90-96% in adults, 97.7% in children
  • Specificity: >95% in adults, 70.2% in children 2, 1
• Measure total serum IgA simultaneously to rule out IgA deficiency 1

Step 2: Management of Special Situations

• If IgA deficient (occurs in 1-3% of celiac patients):
  • Order IgG-based tests: IgG tTG, IgG EMA, or IgG deamidated gliadin peptide (DGP) 2, 1
  • Note: Isolated positive tTG IgG with negative tTG IgA has low utility (only 3% diagnostic yield) 3
• If tTG-IgA is weakly positive:
  • Order IgA endomysial antibody (EMA-IgA) as confirmatory test
  • EMA-IgA has slightly lower sensitivity (88% in adults, 94.5% in children) but higher specificity (99.6% in adults, 93.8% in children) 2, 1

Step 3: Intestinal Biopsy

• Biopsy indication: Required for diagnosis in adults with positive serology 2
• Biopsy procedure:
  • Take multiple (ideally 6) biopsy specimens
  • Obtain from second part of duodenum or beyond (not duodenal bulb)
  • Look for characteristic histologic changes: villous atrophy, crypt lengthening, increased lamina propria and intraepithelial lymphocytes 2

Critical Testing Considerations

Gluten Consumption Requirements

• Maintain regular gluten consumption before testing:
  • Consume 1-3 slices of gluten-containing bread daily
  • Continue for at least 6 weeks prior to testing
  • Do not start gluten-free diet until after biopsy is completed 1

Testing Pitfalls to Avoid

1. Premature gluten restriction: Even partial gluten reduction can reduce lesion severity and lead to false negatives 2, 1
2. Relying on antigliadin antibodies: These have inferior accuracy compared to tTG-IgA and EMA-IgA 1
3. Using at-home tests: These have lower accuracy, limited options, and no professional oversight 1
4. Failing to check IgA levels: IgA deficiency leads to false-negative tTG-IgA results 1

Special Clinical Scenarios

• High clinical suspicion despite negative serology:
  • Test for HLA-DQ2/DQ8 genetic markers
  • If positive, proceed to intestinal biopsy 2
• Very high tTG-IgA levels (≥100 units):
  • Almost exclusively associated with Marsh 3 histopathology (96% of cases)
  • Highly specific for celiac disease 4

Who Should Be Tested

Testing should be considered in:

• Patients with unexplained gastrointestinal symptoms
• Unexplained iron deficiency anemia
• Premature osteoporosis
• Unexplained elevated liver enzymes
• First-degree relatives of celiac patients
• Patients with associated conditions (Type 1 diabetes, autoimmune thyroid disease, Down syndrome) 2, 1

By following this diagnostic algorithm, clinicians can accurately diagnose celiac disease, preventing complications such as osteoporosis, infertility, and small bowel cancer that may occur if the condition remains untreated 1.