What is the workup for celiac disease (CeD) using blood tests, specifically serologic testing?

Workup for Celiac Disease Blood Testing

The first-line serological test for celiac disease is IgA tissue transglutaminase antibody (tTG-IgA), which must be performed while the patient is consuming gluten for at least 6 weeks prior to testing. 1

Initial Serological Testing Algorithm

1. Primary Test: IgA tissue transglutaminase antibody (tTG-IgA)

   • Sensitivity: 90-96% in adults, 97.7% in children
   • Specificity: 87.4% in adults, 70.2% in children
   • Threshold: 15-20 U/mL 2, 1

2. Concurrent Test: Total serum IgA level

   • Must be checked simultaneously with tTG-IgA to rule out IgA deficiency
   • Critical step as IgA deficiency will cause false-negative results on IgA-based tests 1

3. If IgA Deficient: Order IgG-based testing

   • Options include IgG Deamidated Gliadin Peptide (IgG-DGP) or IgG tissue transglutaminase (IgG-tTG)
   • Note: Isolated positive tTG-IgG with negative tTG-IgA has low utility (3%) in diagnosing celiac disease when not IgA deficient 3

Confirmatory Testing

1. IgA Endomysial Antibodies (EMA-IgA)

   • Used as a confirmatory test when tTG-IgA is positive
   • Sensitivity: 88% in adults, 94.5% in children
   • Specificity: 99.6% in adults, 93.8% in children
   • Threshold: 1:5 in adults, 1:10 in children
   • Note: EMA testing is more observer-dependent and not available in all laboratories 2, 1

2. Deamidated Gliadin Peptide Antibodies (DGP)

   • IgA DGP: 96.4% sensitivity in adults
   • IgG DGP: 93.6% sensitivity, 99.4% specificity in adults
   • Useful as additional confirmatory test 2, 1

Important Pre-Testing Requirements

• Patient must maintain regular gluten consumption for at least 6 weeks prior to testing
• Recommended gluten intake: 1-3 slices of gluten-containing bread daily
• Premature gluten restriction can reduce lesion severity and lead to false-negative results 1

HLA Testing Considerations

• HLA-DQ2/DQ8 testing is not a first-line test but useful in specific scenarios:
  • Patients with Down syndrome
  • Equivocal small-bowel histologic findings
  • Patients already on a gluten-free diet
  • Negative HLA-DQ2/DQ8 virtually excludes celiac disease 1

Common Pitfalls to Avoid

1. Inadequate gluten consumption: Ensure patient has been consuming adequate gluten (1-3 slices of bread daily) for at least 6 weeks before testing 1

2. Failure to check total IgA: Always measure total IgA concurrently with tTG-IgA to identify IgA deficiency 1

3. Relying solely on IgG tTG when IgA is normal: Isolated positive IgG tTG with negative IgA tTG has low diagnostic utility (3%) in non-IgA deficient patients 3

4. Diagnosing based on dietary response alone: Improvement on gluten restriction is insufficient for diagnosis; proper serological testing is essential 1

5. Premature gluten restriction: Starting a gluten-free diet before completing testing can lead to false-negative results 1

Remember that positive serological testing should be followed by upper endoscopy with multiple duodenal biopsies (at least 6 specimens from different locations) for definitive diagnosis of celiac disease 1.