What are the causes of elevated gliadin Immunoglobulin A (IgA) levels, particularly in individuals of European descent?

Causes of Elevated Gliadin IgA

Elevated gliadin IgA antibodies are primarily caused by celiac disease, an autoimmune disorder triggered by gluten ingestion in genetically susceptible individuals, though they can also be elevated in active Crohn's disease and other small intestinal inflammatory conditions. 1

Primary Cause: Celiac Disease

• Celiac disease is the most specific and common cause of elevated gliadin IgA antibodies, occurring when the immune system reacts to gliadin (a gluten protein found in wheat, barley, and rye) in genetically predisposed individuals 1
• Gliadin IgA antibodies demonstrate 97-100% sensitivity for detecting untreated celiac disease with flat intestinal mucosa, making them highly indicative of small intestinal disease 2, 3
• The antibody levels correlate with disease activity and decrease significantly when patients adhere to a gluten-free diet, then rise again with gluten challenge 4, 3

Secondary Causes: Other Small Intestinal Diseases

• Active Crohn's disease causes significantly elevated gliadin IgA levels, with patients showing antibody values comparable to those with celiac disease on gluten-containing diets 5
• Cow's milk protein and/or soy protein intolerance with flat intestinal mucosa can produce elevated gliadin IgA antibodies in approximately 75% of cases 3
• The variability in antibody levels suggests that factors beyond gluten intake—such as the degree of intestinal inflammation and mucosal damage—influence antibody production 5

Associated Autoimmune Conditions

• Autoimmune thyroid diseases (chronic thyroiditis and Graves' disease) show elevated gliadin IgA antibodies in 15.98% of patients, significantly higher than the 1312 control blood donors 6
• Patients with chronic thyroiditis treated with high-dose levothyroxine (125-200 mcg daily) demonstrate higher gliadin IgA levels compared to those on lower doses (50-100 mcg daily), suggesting latent celiac disease may impair therapeutic absorption 6
• Type 1 diabetes occurs in 1-16% of celiac patients versus 0.3-1% in the general population, warranting screening in this population 1

Critical Diagnostic Algorithm

When gliadin IgA is elevated, follow this stepwise approach:

1. Measure tissue transglutaminase (tTG) IgA with total serum IgA levels as the preferred confirmatory test, which has 90-96% sensitivity and superior specificity compared to gliadin antibodies alone 1, 7

2. If IgA deficient (occurs in 1-3% of celiac patients), measure IgG-based tests (IgG deamidated gliadin peptide or IgG tTG) instead, as IgA deficiency causes falsely negative IgA-based tests 8, 1

3. Proceed to upper endoscopy with at least 6 duodenal biopsies if tTG-IgA is positive, as biopsy remains the gold standard for diagnosis 1, 9

4. Screen for associated conditions: thyroid function tests, fasting glucose/HbA1c for type 1 diabetes, CBC and iron studies for anemia 1, 9

Important Clinical Pitfalls

• Never interpret gliadin IgA results without measuring total IgA levels, as selective IgA deficiency causes falsely negative IgA-based tests and occurs in 1-3% of celiac disease patients 8, 1
• Gliadin antibodies have lower specificity (62-82%) than tTG or endomysial antibodies, which is why current guidelines prioritize tTG-IgA as the primary screening test rather than gliadin antibodies alone 1, 2
• Patients must consume at least 10g of gluten daily for 6-8 weeks before testing to avoid false-negative results 9
• Never start a gluten-free diet before completing diagnostic workup, as this leads to false-negative serology and inconclusive biopsies 9
• Approximately 17% of children with normal intestinal mucosa may have elevated gliadin antibodies, indicating the test's imperfect specificity 3

Mucosal vs. Systemic Response Patterns

• Serum gliadin IgA antibodies provide the most sensitive (84%) and specific (95%) test for detecting untreated celiac disease and offer early objective indicators of adherence to gluten-free diet 4
• Intestinal aspirate IgA anti-gliadin antibodies remain elevated in both treated and untreated celiac patients, while serum levels decrease with dietary compliance, demonstrating compartmentalized mucosal immune responses 4
• Salivary IgA anti-gliadin antibodies are not increased in celiac patients compared to controls, confirming that different portions of the gastrointestinal tract function as separate immunological organs 4