What does a positive gliadin antibody (IgA) test result indicate?

Gliadin Antibody (IgA) Testing in Celiac Disease Diagnosis

A positive gliadin antibody (IgA) test alone is not sufficient for diagnosing celiac disease and has been largely replaced by more accurate tests like tissue transglutaminase antibody (tTG-IgA), which is now the primary recommended serological test for celiac disease screening. 1

Modern Diagnostic Approach for Celiac Disease

Primary Recommended Testing

• Tissue transglutaminase antibody (tTG-IgA) is the current gold standard serological test with superior sensitivity (97.7%) and specificity (70.2%) in children 1
• Total serum IgA should be measured alongside tTG-IgA to rule out IgA deficiency which can cause false negatives 1
• If tTG-IgA is positive, duodenal biopsies are necessary for confirmation (at least 6 specimens: 1-2 from duodenal bulb and 4+ from distal duodenum) 1

Role of Gliadin Antibodies in Modern Testing

Gliadin antibody testing has evolved significantly:

• Traditional gliadin antibodies (used in older studies) have been largely abandoned due to inferior accuracy 2
• Deamidated gliadin antibodies have better diagnostic performance than traditional gliadin antibodies, with sensitivity of 74% for IgA and 65% for IgG 2
• However, even deamidated gliadin antibodies don't outperform tTG-IgA, which remains the preferred initial test 1, 2

Historical Context of Gliadin Antibody Testing

Earlier research from the 1980s-1990s showed:

• Gliadin IgA antibodies were significantly elevated in untreated celiac disease patients compared to controls 3, 4, 5
• Sensitivity ranged from 84-100% with specificity of 62-95% depending on the cutoff values used 3, 6
• Gliadin antibodies decreased significantly when patients switched from gluten-containing to gluten-free diets 3

Important Clinical Considerations

Potential Pitfalls

• Starting a gluten-free diet before testing reduces sensitivity of both serology and biopsy 1
• IgA deficiency can lead to false-negative results in IgA-based tests (including gliadin IgA) 1
• Gliadin antibodies may be elevated in other gastrointestinal conditions like Crohn's disease, reducing specificity 5

Diagnostic Algorithm

1. Start with tTG-IgA and total serum IgA while patient is on gluten-containing diet
2. If tTG-IgA positive → proceed to duodenal biopsies
3. If tTG-IgA negative but high clinical suspicion → check for IgA deficiency
4. If IgA deficient → use IgG-based testing (tTG-IgG, deamidated gliadin IgG)
5. Consider HLA-DQ2/DQ8 testing in specific scenarios (negative serology with strong suspicion, patients already on gluten-free diet, equivocal biopsy results) 1

In summary, while a positive gliadin IgA test historically suggested possible celiac disease, current guidelines recommend tTG-IgA as the primary serological test due to its superior diagnostic performance. Gliadin antibody testing has been largely replaced in modern clinical practice.