What is the main testing for gluten sensitivity?

Main Testing for Gluten Sensitivity

The primary diagnostic test for gluten sensitivity is IgA tissue transglutaminase antibody (tTG-IgA), which has high sensitivity (90-96%) and specificity (>95%) for celiac disease. 1

Diagnostic Algorithm for Gluten Sensitivity

Initial Testing

• IgA tissue transglutaminase antibody (tTG-IgA) is the most efficient single serologic test for detecting celiac disease in the primary care setting 2, 1
• Testing must be performed while the patient is on a gluten-containing diet to avoid false negative results 1
• IgA endomysial antibody (EMA-IgA) can be used as a second-line test with slightly lower sensitivity but excellent specificity (99.6%) 2, 1

Confirmatory Testing

• Upper endoscopy with small bowel biopsy remains the gold standard for establishing the diagnosis of celiac disease 2
• Multiple duodenal biopsies (one or two from the bulb and at least four from the distal duodenum) are recommended for confirmation 2
• Characteristic histologic findings include a spectrum from partial to total villous atrophy, crypt lengthening, and increased intraepithelial lymphocytes 2

Special Considerations

• In patients with IgA deficiency, IgG-based tests (IgG EMA and/or IgG tTG) should be used instead 2
• HLA-DQ2 and HLA-DQ8 testing has excellent negative predictive value (>99%) and can be useful to rule out celiac disease in select patients 2, 1
• HLA testing is particularly valuable in patients with Down syndrome, equivocal small-bowel histologic findings, or those already on a gluten-free diet without prior testing 2

Differentiating Celiac Disease from Non-Celiac Gluten Sensitivity

• Non-celiac gluten sensitivity is diagnosed only after celiac disease has been ruled out through appropriate testing 2
• Diagnosis of non-celiac gluten sensitivity requires negative celiac serology, normal small bowel histology (in patients not following a gluten-free diet), and HLA-DQ typing to rule out celiac disease 2, 3
• Approximately half of non-celiac gluten sensitivity patients are HLA-DQ2 positive and may have IgG anti-gliadin antibodies 3

Testing Pitfalls and Caveats

• Serologic tests must be performed while the patient is consuming gluten; false negatives occur if testing is done after gluten elimination 1, 4
• Lymphocytic infiltration of intestinal epithelium without villous atrophy is not specific for celiac disease and requires consideration of other causes (H. pylori infection, small bowel bacterial overgrowth, autoimmune disorders) 2
• Tests not recommended for celiac disease diagnosis include stool studies, small-bowel follow-through, intestinal permeability testing, D-xylose testing, and salivary testing 2
• Antigliadin antibody tests (especially IgG-based) have poor sensitivity and specificity and are no longer recommended for initial screening 2, 5

Testing in Special Populations

• In children under 2 years, combining tTG-IgA with IgG and IgA deamidated gliadin peptides is recommended for improved sensitivity 1
• Recent guidelines suggest children with tTG-IgA ≥10× upper limit of normal, positive EMA-IgA, and positive HLA may avoid biopsy 1
• Consider testing in high-risk groups: those with iron deficiency anemia, premature osteoporosis, Down syndrome, unexplained liver enzyme elevations, type 1 diabetes, first-degree relatives of celiac patients, and autoimmune thyroid disease 1

Testing After Gluten-Free Diet Initiation

• If a patient has been following a gluten-free diet for less than one month, serologic and histologic findings may still be abnormal and useful for diagnosis 2
• For patients already on a gluten-free diet without prior testing, gluten challenge testing is the preferred diagnostic approach in HLA-DQ2 and HLA-DQ8 positive patients 2
• HLA-DQ2 and HLA-DQ8 testing is particularly valuable in patients already on a gluten-free diet, as these genetic markers remain unchanged regardless of diet 2, 1