What is the difference between endomysial antibodies (EMA) and gliadin antibodies in diagnosing celiac disease?

Endomysial vs. Gliadin Antibodies in Celiac Disease Diagnosis

Endomysial antibodies (EMA) are superior to gliadin antibodies for diagnosing celiac disease, with EMA-IgA demonstrating higher specificity (93.8% in children, up to 100% in adults) compared to traditional gliadin antibodies, which have been largely replaced by deamidated gliadin peptide antibodies (DGP) in modern testing. 1, 2

Key Differences Between Antibody Tests

Endomysial Antibodies (EMA)

• Target: Autoantibodies that target the endomysium (connective tissue surrounding muscle fibers)
• Performance:
  • Specificity: Extremely high (93.8% in children, 99.6% in adults) 1, 2
  • Sensitivity: Very good (94.5% in children) 2
  • False negative rate: Only about 1% 1
• Clinical use: Often used as a confirmatory test following positive tTG-IgA results
• Production site: Small intestinal mucosa of celiac patients 3

Gliadin Antibodies

• Traditional anti-gliadin antibodies (AGA):

  • Lower specificity and sensitivity than EMA
  • Largely replaced by newer tests
  • No longer recommended as first-line testing

• Deamidated Gliadin Peptide Antibodies (DGP):

  • Modern replacement for traditional gliadin antibodies
  • Better performance than traditional AGA
  • IgG DGP: Very high specificity (98.9%) 4
  • Particularly useful in IgA-deficient patients 2, 4

Diagnostic Algorithm for Celiac Disease

1. First-line testing:

   • IgA tissue transglutaminase (tTG-IgA) with total IgA level 2

2. If tTG-IgA positive:

   • Confirm with EMA-IgA testing (from a second blood sample)
   • When tTG-IgA >10× upper limit of normal + positive EMA-IgA: PPV approaches 100% 2

3. If IgA deficiency present:

   • Use IgG DGP and IgG tTG instead 2, 4

4. Biopsy considerations:

   • Multiple duodenal biopsies (4-6) while on gluten-containing diet
   • Look for: increased intraepithelial lymphocytes, crypt hyperplasia, villous atrophy 2

Clinical Pearls and Pitfalls

• Early-stage disease detection: DGP-AGA may be useful in early-stage celiac disease when villous architecture is still normal (Marsh I-II), with sensitivity comparable to EMA (79% vs. 81%) 5

• Subclinical/silent disease: Both antibody types show lower prevalence in mild cases:

  • EMA positivity: 0% in Marsh I, 40% in Marsh II, increasing to >80% in more severe cases 6
  • AGA positivity: 0-30% in Marsh I-II, increasing with disease severity 6

• Common pitfall: Relying solely on antibody testing in mild or early disease may lead to false negatives

  • Biopsy remains the gold standard, especially in high-risk patients with mild symptoms 6

• Optimal testing strategy: Combining IgA tTG and IgG DGP provides the best diagnostic accuracy, identifying nearly all celiac cases with very high specificity 4

• Monitoring: After diagnosis, antibody levels should be measured at 6 months, 12 months, and annually thereafter to monitor adherence to gluten-free diet 2

Genetic Testing Context

• HLA-DQ2/DQ8 testing has excellent negative predictive value (approaching 100%)
• Negative HLA testing effectively rules out celiac disease (<1% of celiac patients lack these markers) 2
• However, positive genetic testing alone cannot confirm diagnosis due to low positive predictive value 2