What is the recommended approach for serology testing in suspected celiac disease?

Recommended Approach for Serology Testing in Suspected Celiac Disease

The recommended initial serological test for suspected celiac disease is IgA-tissue transglutaminase (IgA-tTG) antibody testing along with total IgA measurement to rule out IgA deficiency. 1

Initial Diagnostic Testing Algorithm

1. First-line testing:

   • IgA-tissue transglutaminase (IgA-tTG) antibody test
   • Simultaneous total IgA level measurement

2. Interpretation based on IgA status:

   • Normal IgA levels:

     • Positive IgA-tTG: Proceed to duodenal biopsy
     • Negative IgA-tTG: Celiac disease unlikely (high sensitivity of 90-96% in adults) 1

   • IgA deficiency:

     • Use IgG-based testing instead:
       • IgG-deamidated gliadin peptide (IgG-DGP)
       • IgG-tissue transglutaminase (IgG-tTG)
       • IgG endomysial antibodies (IgG-EMA) 1, 2

Confirmatory Testing

• Duodenal biopsy via upper endoscopy remains the gold standard for diagnosis 1
• Critical point: Patient must remain on a gluten-containing diet before biopsy to avoid false-negative results 1
• Multiple biopsies (at least 4-6) from different parts of the duodenum are required 1

Special Considerations for IgA Deficiency

• IgA deficiency is 10-15 times more common in celiac disease patients than in healthy individuals 2
• For IgA-deficient patients, IgG-based antibody tests are highly effective:
  • IgG endomysial antibodies show excellent specificity for celiac disease in IgA-deficient patients 2
  • IgG gliadin antibodies are useful in this population 2
  • IgG tissue transglutaminase antibodies have high sensitivity in IgA-deficient patients with celiac disease 2

Important Diagnostic Pitfalls to Avoid

1. Starting a gluten-free diet before testing

   • This can lead to false-negative serological results and biopsy findings 1

2. Relying solely on IgA-tTG without checking total IgA levels

   • Missing IgA deficiency can lead to false-negative results in celiac patients 1

3. Using IgG-tTG in patients with normal IgA levels

   • This has poor utility (only 3% diagnostic yield) when IgA-tTG is negative in patients with normal IgA levels 3

4. Inadequate biopsy sampling

   • Taking too few samples or from limited locations can lead to missed diagnosis 1

5. Relying solely on symptoms for diagnosis

   • Celiac disease presents with varied and sometimes non-specific symptoms 1, 4

Quantitative Antibody Levels and Biopsy Decision

In specific circumstances, very high antibody titers may be diagnostic without biopsy:

• IgA-tTG titers >118 U identify celiac disease with only 2% false-positive rate 5
• IgA-tTG levels between 21-118 U, combined with an EMA dilution titer ≥1:160, have a positive predictive value of 83% 5
• Conversely, IgA-tTG <20 U with EMA dilution titer <1:10 has a negative predictive value of 92% 5

Monitoring After Diagnosis

• Anti-tTG antibody levels should be measured at 6 months, 12 months, and annually thereafter to monitor adherence to gluten-free diet 1
• Persistently positive or non-decreasing anti-tTG levels strongly indicate poor adherence or ongoing gluten exposure 1