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 other small intestinal diseases, particularly active Crohn's disease. 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). 1, 2
Diagnostic Context in Celiac Disease
Screen for celiac disease by measuring IgA tissue transglutaminase (tTG) antibodies with documentation of normal total serum IgA levels, as this is the preferred first-line test with 90-96% sensitivity. 1, 3
If IgA deficient (which occurs in 1-3% of celiac patients), measure IgG to tTG and deamidated gliadin antibodies instead, as IgA deficiency causes falsely negative IgA-based tests. 1, 4
Gliadin antibodies can remain elevated in celiac patients even on a gluten-free diet for up to 18 months, with 17 of 30 asymptomatic patients showing persistent elevation in one study. 5
The specificity of gliadin antibodies is lower than tTG or endomysial antibodies, which is why current guidelines prioritize tTG-IgA as the primary screening test rather than gliadin antibodies alone. 1, 3
Secondary Causes: Other Intestinal Diseases
Active Crohn's Disease
Patients with active Crohn's disease demonstrate significantly elevated IgA antibodies to gliadin compared to healthy controls, though typically not as high as in celiac disease. 6
The elevation reflects small intestinal inflammation and increased intestinal permeability, not an autoimmune response to gluten. 6
Ulcerative Colitis
- No significant correlation exists between ulcerative colitis disease activity and gliadin IgA antibody levels. 6
Associated Autoimmune Conditions
When gliadin IgA is elevated in the context of celiac disease, assess for commonly associated autoimmune disorders:
Type 1 diabetes (occurs in 1-16% of celiac patients versus 0.3-1% in general population) 1
Autoimmune thyroid disease (occurs in 17-30% of type 1 diabetes patients who also have celiac disease) 1
IgA nephropathy (rare but documented association where gluten-free diet can lead to remission of nephrotic syndrome) 7
Addison's disease, autoimmune hepatitis, and other autoimmune conditions occur more frequently with celiac disease 1
Genetic and Environmental Factors
The G2m(n) immunoglobulin heavy chain allotype marker is present in 94% (16 of 17) of celiac patients with elevated antigliadin antibodies. 5, 8
HLA-B8 or HLA-DR3 serologic specificities are present in 82% (14 of 17) of celiac patients with elevated antibody titers. 5
Gliadin antibodies can be directed against one or multiple gliadin fractions (alpha, beta, gamma, omega), with 71% of positive patients showing reactivity to multiple fractions. 5
Critical Diagnostic Pitfalls
Never interpret gliadin IgA results without measuring total IgA levels, as selective IgA deficiency (1-3% of celiac patients) causes falsely negative IgA-based tests. 1, 4
Patients must consume at least 10g of gluten daily for 6-8 weeks before testing to avoid false-negative results. 4, 3
Do not start a gluten-free diet before completing diagnostic workup (including biopsy if indicated), as this leads to false-negative serology and inconclusive biopsies. 4, 3
High levels of IgA antibodies to gliadin are indicative of small intestinal disease, but variability exists based on gluten intake amount and other unidentified factors. 6
Recommended Diagnostic Algorithm
- Confirm elevated gliadin IgA with tTG-IgA and total IgA measurement 1
- If tTG-IgA elevated, add endomysial antibody (EMA) testing (99.6% specificity) for confirmation 4, 3
- Proceed to upper endoscopy with at least 6 duodenal biopsies if antibodies positive 1, 3
- Screen for associated autoimmune conditions (thyroid function, fasting glucose/HbA1c) 1
- Evaluate for nutritional deficiencies (CBC, iron studies, vitamin levels) 3