Blood Tests to Rule Out Celiac Disease
Order IgA tissue transglutaminase (tTG-IgA) antibody testing along with total IgA level measurement as your initial diagnostic blood work for celiac disease. 1
Primary Serologic Testing
The first-line blood test panel should include:
- IgA tissue transglutaminase (tTG-IgA) - This is the preferred initial screening test with 90.7% sensitivity and 87.4% specificity in adults at the 15 U/mL threshold 1
- Total IgA level - This must be measured simultaneously to identify IgA deficiency, which occurs in 1-3% of celiac patients and causes falsely negative IgA-based tests 2, 1
This two-test approach is critical because if your patient has selective IgA deficiency (which is more common in celiac disease), the tTG-IgA will be falsely negative despite active disease 2, 1.
If IgA Deficiency is Detected
When total IgA is low or deficient, immediately order IgG-based tests:
- IgG deamidated gliadin peptide (DGP-IgG) - This is the preferred IgG test with superior diagnostic accuracy of 93.6% sensitivity and 99.4% specificity 1, 3
- IgG tissue transglutaminase (tTG-IgG) can be used as an alternative, though it has lower accuracy with only 40.6-84.6% sensitivity 1
Confirmatory Serologic Testing
If tTG-IgA is positive, consider adding:
- IgA endomysial antibody (EMA) - This serves as confirmatory testing with excellent specificity of 99.6% in adults and should be performed when tTG-IgA is elevated 2, 3
The combination of positive tTG-IgA and positive EMA has virtually 100% positive predictive value for celiac disease 3.
Critical Pre-Testing Requirements
Your patient must be consuming adequate gluten at the time of testing - at least 10g of gluten daily (equivalent to approximately 3 slices of wheat bread) for 6-8 weeks prior to blood draw to avoid false-negative results 2, 1. Given that your patient has a history of gluten avoidance due to food allergies, this is a crucial consideration. If she has already eliminated gluten, testing will be unreliable and she would need to reintroduce gluten for 1-3 months before testing 2.
What NOT to Order Initially
- HLA-DQ2/DQ8 genetic testing - This is not part of routine initial screening and should only be considered in specific scenarios such as patients with equivocal serologic or histologic findings, or those already on a gluten-free diet before diagnostic workup 1
- The negative predictive value exceeds 99% when both HLA-DQ2 and HLA-DQ8 are absent, effectively ruling out celiac disease, but this is reserved for specific diagnostic dilemmas 1
Next Steps After Positive Serology
Blood tests alone cannot diagnose celiac disease in adults. Upper endoscopy with small bowel biopsy is mandatory to confirm the diagnosis in patients with positive serology, requiring at least 1-2 biopsies from the duodenal bulb and 4-6 biopsies from the second part of the duodenum or beyond 1, 4.
Special Considerations for This Patient
Given your patient's age (23 years old, female) and history of food allergies including gluten:
- First-degree relatives of celiac patients should be screened even without symptoms, so inquire about family history 1
- Women have a 2:1 higher prevalence of celiac disease compared to men 2
- If she has already been avoiding gluten due to perceived "allergy," distinguish between true celiac disease (which requires lifelong strict adherence and monitoring) versus non-celiac gluten sensitivity (which has different implications) 2
Common Pitfalls to Avoid
- Never start a gluten-free diet before completing diagnostic workup - this leads to false-negative serology and inconclusive biopsies 2, 3
- Do not rely on symptoms alone or symptom response to gluten-free diet for diagnosis, as this cannot differentiate celiac disease from non-celiac gluten sensitivity 3
- Do not skip measuring total IgA level - approximately 1-3% of celiac patients have IgA deficiency which would render all IgA-based tests falsely negative 2, 1