What labs are used to test for celiac disease?

Laboratory Tests for Celiac Disease Diagnosis

The most efficient initial laboratory tests for diagnosing celiac disease are total immunoglobulin A (IgA) and IgA tissue transglutaminase antibody (tTG-IgA). 1

Primary Serological Testing

First-Line Testing

• IgA tissue transglutaminase antibody (tTG-IgA)

  • Most sensitive and specific initial test
  • Sensitivity: 90-96% in adults, 97.7% in children 1
  • Specificity: >95% in adults, 70.2% in children 1
  • Should be performed while patient is on a gluten-containing diet

• Total serum IgA level

  • Should be measured concurrently with tTG-IgA
  • Essential to rule out IgA deficiency, which occurs in a small percentage of celiac patients
  • IgA deficiency would cause false-negative tTG-IgA results 1

Second-Line Testing (Based on Initial Results)

• IgA endomysial antibody (EMA-IgA)

  • Used when tTG-IgA is weakly positive
  • Excellent specificity (99.6%) but slightly lower sensitivity than tTG-IgA 1
  • More time-consuming and operator-dependent than tTG-IgA
  • Particularly useful as a confirmatory test

• For IgA-deficient patients:

  • IgG deamidated gliadin peptide (DGP-IgG)
  • IgG tissue transglutaminase (tTG-IgG)
  • IgG endomysial antibody (EMA-IgG) 1

Testing Algorithm

1. Initial screening: tTG-IgA and total serum IgA
2. If tTG-IgA is weakly positive: Add EMA-IgA testing
3. If tTG-IgA is negative but suspicion remains high:
   • Check total IgA level
   • If IgA deficient: Order IgG-based tests (tTG-IgG, EMA-IgG, or DGP-IgG)
   • Consider HLA-DQ2/DQ8 genetic testing
4. If tTG-IgA is strongly positive (>10x upper limit of normal):
   • Add EMA-IgA testing
   • When both are positive, positive predictive value approaches 100% 1

Important Considerations

• Maintain gluten in diet before testing

  • Patients must consume a gluten-containing diet for at least 6 weeks prior to testing
  • Premature gluten restriction can lead to false-negative results 1
  • If already on gluten-free diet, recommend 3 slices of wheat bread daily for 1-3 months before testing 1

• Incomplete concordance between tests

  • Some patients may be positive for only tTG-IgA or only EMA-IgA
  • Using both tests increases sensitivity to approximately 93% 2
  • About 7% of celiac patients may be negative for both antibodies despite having the disease 2

• Biopsy remains the gold standard

  • Serological tests are used for initial screening
  • Positive serological tests should be followed by duodenal biopsy for definitive diagnosis
  • Multiple biopsy specimens (ideally 6) should be obtained from the second part of the duodenum or beyond 1

Limitations of Serological Testing

• Serological tests have limited utility in monitoring patients already on gluten-free diets
• tTG-IgA and EMA-IgA have low sensitivity (<50%) for detecting persistent villous atrophy in patients following a gluten-free diet 3
• Some celiac patients with normal IgA levels may still be seronegative, particularly those with milder intestinal damage 2, 4

Early and accurate diagnosis is crucial as untreated celiac disease can lead to serious complications including osteoporosis, infertility, and increased risk of small bowel cancer 1.