What lab test is used to check for gluten sensitivity or celiac disease?

Laboratory Testing for Celiac Disease

The IgA tissue transglutaminase antibody (tTG-IgA) is the preferred first-line screening test for celiac disease, with sensitivity of 90-96% and specificity >95%. 1, 2

Primary Screening Test

• IgA tissue transglutaminase antibody (tTG-IgA) should be ordered as the initial test in patients over 2 years of age, as it supplants older gliadin antibody testing. 1
• Total IgA level must be measured simultaneously to rule out IgA deficiency, which occurs in 1-3% of celiac disease patients and would cause false-negative results. 2, 3
• Testing must be performed while the patient is consuming a gluten-containing diet (at least 10g daily for 6-8 weeks) to avoid false-negative results. 2, 3

Confirmatory Serologic Testing

• When tTG-IgA levels are >10× the upper limit of normal, IgA endomysial antibody (EMA-IgA) should be performed as a confirmatory test with excellent specificity of 99.6%. 2, 3
• The combination of markedly elevated tTG-IgA (>10× upper limit) plus positive EMA-IgA approaches 100% positive predictive value for celiac disease. 2

Testing in IgA-Deficient Patients

• If IgA deficiency is detected, switch to IgG-based tests: IgG deamidated gliadin peptide (DGP-IgG) or IgG tissue transglutaminase (tTG-IgG). 2, 3
• IgG-based tests are markedly less accurate in patients with normal IgA levels and should not be used in that setting. 1, 2

Special Pediatric Considerations

• In children under 2 years of age, tTG-IgA testing should be combined with IgG and IgA deamidated gliadin peptides to improve sensitivity. 1, 3

Genetic Testing

• HLA-DQ2 and HLA-DQ8 testing has >99% negative predictive value—absence of both alleles essentially rules out celiac disease. 2, 3
• HLA testing is useful when celiac disease is strongly suspected despite negative serology, in patients with equivocal biopsy findings, or in patients already on a gluten-free diet who were never properly tested. 2

Gold Standard Confirmation

• Upper endoscopy with small bowel biopsy remains the gold standard for diagnosis in adults, with multiple specimens (ideally 6 biopsies: 1-2 from duodenal bulb and at least 4 from second part of duodenum or beyond) required. 2, 3
• Characteristic histologic findings include villous atrophy, crypt lengthening, and increased intraepithelial lymphocytes. 1, 2

Tests That Should NOT Be Used

• IgA and IgG antigliadin antibodies are no longer recommended for primary detection, as they have inferior diagnostic performance compared to tTG-IgA and EMA. 1
• Combining multiple serologic tests instead of tTG-IgA alone may marginally increase sensitivity but reduces specificity and is not recommended in low-risk populations. 1

Critical Pitfall to Avoid

• Never initiate a gluten-free diet before completing diagnostic testing, as this leads to false-negative serology and inconclusive biopsies. 2, 3
• Patients who have already started a gluten-free diet must resume normal diet with three slices of wheat bread daily for 1-3 months before repeat testing. 2