What test is used to check for gluten intolerance?

Diagnostic Testing for Gluten Intolerance

The primary test for gluten intolerance (celiac disease) is the IgA tissue transglutaminase antibody (tTG-IgA) test, which should be performed while the patient is on a gluten-containing diet. 1

Initial Diagnostic Testing

The recommended diagnostic approach follows this algorithm:

1. First-line serological testing:

   • IgA tissue transglutaminase antibody (tTG-IgA) - sensitivity 97.7% in children 1
   • Total serum IgA levels (to rule out IgA deficiency) 1

2. For children under 2 years:

   • Combine tTG-IgA with IgG and IgA deamidated gliadin peptides for improved sensitivity 1

3. If serological tests are positive:

   • Upper endoscopy with multiple duodenal biopsies (gold standard) 1
   • At least 6 specimens should be collected: 1-2 from the bulb and at least 4 from the distal duodenum 1

Special Considerations

• IgA deficiency: If total IgA is low, alternative testing should be used as tTG-IgA may be falsely negative 1

• Genetic testing (HLA-DQ2/DQ8):

  • Not recommended for routine diagnosis
  • Useful in specific situations:
    • Seronegative cases with suspected celiac disease
    • Equivocal small-bowel histologic findings
    • Patients already following a gluten-free diet
    • Discrepant celiac-specific serology and histology 1
  • Negative HLA-DQ2 and HLA-DQ8 results have >99% negative predictive value, making celiac disease highly unlikely 1

Non-Celiac Gluten Sensitivity Testing

For non-celiac gluten sensitivity (NCGS), the serological pattern differs from celiac disease:

• IgG anti-gliadin antibodies (AGA) may be positive in about 56.4% of cases
• IgA AGA may be positive in a small percentage (7.7%)
• tTG-IgA, endomysial antibodies (EmA), and deamidated gliadin peptide antibodies (DGP-AGA) are typically negative 2

Important Caveats

• Timing is critical: Testing must be performed while the patient is consuming gluten; otherwise, false negatives may occur 1

• Limitations of serological tests for follow-up: tTG-IgA and EmA-IgA have low sensitivity (<50%) for detecting persistent villous atrophy in patients already on a gluten-free diet 3

• High antibody titers: An anti-TTG ratio ≥7 times the upper limit of normal has high specificity for intestinal damage, while a ratio >20 is highly specific (99.8%) for villous atrophy 4

• Inadequate biopsy sampling can lead to missed diagnosis, highlighting the importance of proper sampling techniques 1

High-Risk Populations

Consider testing in high-risk individuals even without symptoms:

• First-degree relatives (7.5% risk)
• Patients with type 1 diabetes
• Autoimmune thyroid disease
• Down syndrome
• Turner syndrome
• Unexplained iron deficiency anemia 1