Complete Celiac Panel: Initial Diagnostic Testing
For patients suspected of having celiac disease, order IgA tissue transglutaminase (tTG-IgA) antibody testing along with total IgA level measurement as the initial diagnostic step. 1, 2
Recommended Initial Serologic Panel
The complete celiac panel should include:
- IgA tissue transglutaminase (tTG-IgA) - This is the preferred first-line screening test with 90.7% sensitivity and 87.4% specificity in adults at 15 U/mL threshold 2, 3
- Total IgA level - Essential to identify IgA deficiency, which occurs in 1-3% of celiac patients and causes falsely negative IgA-based tests 1, 2, 4
- IgA endomysial antibody (EMA) - Serves as confirmatory testing with excellent specificity of 99.6% when tTG-IgA is elevated 1, 2
Critical Pre-Test Requirements
Patients must be consuming adequate gluten (at least 10g daily) at the time of testing to avoid false-negative results 2, 5. Testing should never be performed after the patient has already started a gluten-free diet, as this leads to inconclusive results 2, 5.
Algorithm for IgA-Deficient Patients
If total IgA is low or deficient (typically <7 mg/dL):
- Order IgG-based tests immediately - IgG deamidated gliadin peptide (DGP-IgG) is preferred with 93.6% sensitivity and 99.4% specificity 2, 4
- Alternative: IgG tissue transglutaminase (tTG-IgG) - Though less accurate than DGP-IgG, with only 40.6-84.6% sensitivity 2, 4
Confirmatory Diagnostic Step
Upper endoscopy with small bowel biopsy is mandatory to confirm the diagnosis in patients with positive serology 1, 3. The biopsy protocol should include:
- At least 1-2 biopsies from the duodenal bulb 1
- At least 4-6 biopsies from the second part of the duodenum or beyond 1, 2, 4
- Specimens must be properly oriented for histologic analysis using Marsh classification 2
When to Consider HLA Testing
HLA-DQ2 and HLA-DQ8 genetic testing is not part of routine initial screening but should be considered in specific scenarios 1:
- Patients with equivocal serologic or histologic findings 1
- Patients already on a gluten-free diet before diagnostic workup 1
- Discordant serology and biopsy results 1
- First-degree relatives of celiac patients for risk stratification 2
The negative predictive value exceeds 99% when both HLA-DQ2 and HLA-DQ8 are absent, effectively ruling out celiac disease 1, 2.
Common Diagnostic Pitfalls to Avoid
- Never start a gluten-free diet before completing the diagnostic workup - This is the most common error leading to false-negative results and inconclusive biopsies 2, 5
- Do not rely on symptoms alone - Gastrointestinal symptoms cannot accurately differentiate celiac disease from other disorders 1
- Do not skip total IgA measurement - Failing to identify IgA deficiency leads to missed diagnoses in 1-3% of celiac patients 2, 4
- Do not order IgG tests routinely - IgG-based testing is only indicated when IgA deficiency is confirmed 2, 4
Special Populations Requiring Screening
Even in the absence of symptoms, screening should be performed in 6, 7:
- First-degree relatives of patients with celiac disease 6, 7
- Patients with type 1 diabetes 6, 7
- Patients with Down syndrome 1, 6
- Unexplained iron deficiency anemia 2, 6
- Unexplained elevated liver transaminases 6, 7
- Premature osteoporosis 5, 7
Interpretation of Highly Elevated tTG-IgA
When tTG-IgA levels exceed 10 times the upper limit of normal, this correlates strongly with severe intestinal damage and has virtually 100% positive predictive value for celiac disease 2. In pediatric patients meeting specific criteria (tTG-IgA >10× upper limit of normal plus positive EMA in a second sample), biopsy may be avoided 7, though this approach is not recommended for adults 1, 3.