How to Test for Celiac Disease
Begin with IgA tissue transglutaminase antibody (tTG-IgA) testing while the patient is on a gluten-containing diet, followed by intestinal biopsy for confirmation in adults. 1, 2
Initial Serologic Testing
- Order IgA tTG as the single most efficient first-line test, with sensitivity of 90.7% and specificity of 87.4% in adults, and 97.7% sensitivity with 70.2% specificity in children 1, 2
- Simultaneously measure total IgA levels to rule out IgA deficiency, which occurs in 1-3% of celiac patients and causes falsely negative results 1, 2
- Ensure the patient is consuming adequate gluten (at least 10g daily for 6-8 weeks) before testing, as gluten restriction causes false-negative results 2, 3
Confirmatory Serologic Testing
- If tTG-IgA is weakly positive in adults, add IgA endomysial antibody (EMA) testing, which has excellent specificity of 99.6% 1
- If tTG-IgA is >10× upper limit of normal, perform EMA-IgA as confirmatory testing—this combination approaches 100% positive predictive value 1, 2
Testing in IgA-Deficient Patients
- Use IgG-based tests if IgA deficiency is confirmed: IgG deamidated gliadin peptide (DGP-IgG) or IgG tTG 1
- Do not use IgG tests in patients with normal IgA levels, as they are markedly less accurate in this setting 1, 2
- Avoid IgA/IgG antigliadin antibody tests, as they provide no additional diagnostic benefit and have poor performance compared to tTG and EMA 1
Intestinal Biopsy (Gold Standard)
- Refer all seropositive adults for upper endoscopy with duodenal biopsy to confirm diagnosis 1
- Obtain at least 6 biopsy specimens: 1-2 from the duodenal bulb and at least 4 from the second part of the duodenum or beyond, as mucosal changes can be patchy 1, 2
- Look for characteristic histologic findings: villous atrophy (total or partial), crypt lengthening with increased lamina propria, and increased intraepithelial lymphocytes 1
- Do not rely on visual endoscopic examination alone, as it is not sufficiently sensitive for detecting celiac disease 1
Biopsy-Avoidance Strategy in Children
- Children with tTG-IgA ≥10× upper limit of normal, positive EMA-IgA, and positive HLA-DQ2/DQ8 may avoid biopsy according to recent pediatric guidelines 1, 2
- Adults still require biopsy confirmation despite high antibody levels, though COVID-19 pandemic protocols temporarily allowed non-biopsy diagnosis in select cases 1
HLA Genetic Testing
- Use HLA-DQ2/DQ8 testing when celiac disease is strongly suspected despite negative serology, as absence of both alleles has >99% negative predictive value and essentially rules out celiac disease 1, 2
- HLA testing is also useful in patients with equivocal biopsy findings or those already on a gluten-free diet without prior testing 2, 3
Special Testing Considerations in Children Under 2 Years
- Combine tTG-IgA with IgG and IgA deamidated gliadin peptides to improve sensitivity in this age group 2, 3
Critical Pitfalls to Avoid
- Never start a gluten-free diet before completing diagnostic testing, as this leads to false-negative serology and inconclusive biopsies 1, 2
- Do not rely solely on serology without biopsy confirmation in adults, as this can lead to misdiagnosis 1, 3
- If the patient has already started a gluten-free diet, they must resume normal diet with three slices of wheat bread daily for 1-3 months before repeat testing 2, 3
- Obtain biopsy specimens promptly after positive serology and instruct patients not to avoid gluten until after specimens are obtained 1
Algorithm for Negative Serology with High Clinical Suspicion
- Confirm adequate gluten intake (at least 10g daily for 6-8 weeks) 2, 3
- Verify total IgA level is normal to rule out IgA deficiency 1, 2
- Perform HLA-DQ2/DQ8 testing—if positive, proceed to biopsy despite negative serology 1, 2
- Alternatively, proceed directly to upper endoscopy and biopsy if signs and symptoms warrant the procedure 1