What do celiac serologies check for?

Celiac Disease Serological Testing

Celiac disease serologies primarily check for antibodies against tissue transglutaminase (tTG), endomysial antibodies (EMA), and deamidated gliadin peptides (DGP), which are key biomarkers for diagnosing celiac disease. 1

Primary Serological Tests

• IgA Tissue Transglutaminase (tTG-IgA):

  • First-line screening test with sensitivity of 90-96% in adults and 97.7% in children 1
  • Uses a threshold of 15-20 U/mL depending on the laboratory 2
  • High specificity (83% in adults) but can produce false positives 2

• IgA Endomysial Antibodies (EMA-IgA):

  • Confirmatory test with sensitivity of 88% in adults and 94.5% in children 2, 1
  • Extremely high specificity of 99.6% in adults and 93.8% in children 2
  • Used as a confirmatory test when tTG-IgA is weakly positive 1
  • Measured using immunofluorescence with thresholds typically at 1:5 for adults and 1:10 for children 2

• Deamidated Gliadin Peptide Antibodies (DGP):

  • IgA DGP: 96.4% sensitivity in adults 2
  • IgG DGP: 93.6% sensitivity with 99.4% specificity in adults 2
  • Particularly useful in IgA-deficient patients 1

Testing Algorithm

1. Initial Screening: Order tTG-IgA as the primary screening test 1

2. Total IgA Level: Always check total IgA levels to rule out IgA deficiency 1

3. If tTG-IgA is weakly positive: Order EMA-IgA as a confirmatory test 1

4. If IgA deficient: Order IgG-based tests (IgG-tTG, IgG-EMA, or IgG-DGP) 1

5. If high clinical suspicion despite negative serology: Consider HLA-DQ2/DQ8 genetic testing 1

Important Considerations

• Patient Preparation: Patients must maintain regular gluten consumption (1-3 slices of bread daily) for at least 6 weeks prior to testing 1

• False Negatives: Premature gluten restriction can lead to false-negative results 1

• Combined Testing: Dual positivity for tTG-IgA and EMA-IgA has a positive predictive value of 97% 3

• Diagnostic Confirmation: Despite high sensitivity of serological tests, duodenal biopsy remains the gold standard for definitive diagnosis 1, 4

• Monitoring Limitations: Serological tests have low sensitivity (<50%) for detecting persistent villous atrophy in patients already on gluten-free diets 5

Pitfalls to Avoid

• Avoid Antigliadin Antibodies (AGA): These older tests have inferior accuracy compared to newer serological markers 1

• Avoid At-Home Testing: These have lower accuracy and no professional oversight 1

• Don't Test While on Gluten-Free Diet: This significantly reduces test sensitivity 1, 5

• Don't Rely Solely on Serology for Follow-Up: Serological tests have poor sensitivity for detecting persistent villous atrophy in treated patients 5

• Don't Overlook IgA Deficiency: This can cause false-negative results in IgA-based tests 1

Accurate serological testing is crucial for timely diagnosis to prevent complications such as osteoporosis, infertility, growth failure in children, and increased risk of small bowel cancer 1, 4.