What are the implications of a low Immunoglobulin A (IgA) level on a celiac disease test?

Low Immunoglobulin A on Celiac Test: Implications and Management

A low IgA level on a celiac disease test requires IgG-based testing to avoid missing celiac disease, as IgA deficiency occurs 10-15 times more frequently in celiac patients than in the general population. 1, 2

Understanding IgA Deficiency in Celiac Testing

IgA deficiency has significant implications for celiac disease testing:

• IgA deficiency occurs in approximately 0.75% of patients tested for celiac disease (1:131 patients) 3
• Celiac disease is found in approximately 1:6 IgA-deficient patients who are properly evaluated 3
• Standard celiac serological tests (IgA anti-tissue transglutaminase, IgA anti-endomysial antibodies) will be falsely negative in IgA-deficient patients 1, 2

Diagnostic Algorithm for Low IgA on Celiac Test

1. Confirm IgA deficiency:

   • Total IgA levels below the lower limit of detection indicate selective IgA deficiency 1

2. Order appropriate alternative tests:

   • IgG-based testing should be performed:
     • IgG against tissue transglutaminase (tTG-IgG)
     • IgG against deamidated gliadin peptide (DGP-IgG)
     • IgG endomysial antibody (EMA-IgG) 1, 2

3. Interpret results correctly:

   • Patients with total IgA levels below detection limit AND positive IgG-based tests should be considered to have celiac disease with selective IgA deficiency 1
   • Note that isolated positive tTG-IgG with negative other markers has low utility (only 3% diagnostic yield) 4

4. Proceed to duodenal biopsy:

   • Even with negative serology, if clinical suspicion is high, duodenal biopsy should be performed 1, 5
   • At least 6 biopsy specimens should be collected from both the duodenal bulb and distal duodenum 2

Common Pitfalls to Avoid

1. Missing celiac disease diagnosis:

   • Up to 2-3% of celiac patients may have negative serology 2
   • Inadequate evaluation of IgA deficiency frequently results in underdiagnosis of both IgA deficiency and celiac disease 3

2. Relying solely on IgA-based tests:

   • Studies show that IgG antibody tests for endomysium, gliadin, and tissue transglutaminase are useful for identifying IgA-deficient patients with celiac disease 6
   • All 15 IgA-deficient patients with celiac disease in one study were positive for EMA-IgG and IgG gliadin antibodies 6

3. Failing to consider genetic testing:

   • HLA-DQ2/DQ8 testing can be valuable in IgA-deficient patients
   • Negative results can be used to rule out celiac disease in seronegative patients 1

4. Inadequate follow-up:

   • Patients with suspected celiac disease who are seronegative but have villous atrophy and genetic risk factors should undergo endoscopic evaluation after 1-3 years on a gluten-free diet 1

Clinical Considerations

• IgA deficiency is 10-15 times more common in celiac disease patients than in healthy subjects 6
• Patients with IgA deficiency and celiac disease may have higher incidence of silent forms (13%), recurrent infections (29.6%), and atopic diseases (13%) 5
• First-degree relatives of celiac patients have a 7.5% risk of celiac disease, highlighting the importance of considering family history 2

By following this systematic approach to evaluating low IgA on celiac testing, clinicians can avoid missing this important diagnosis and ensure appropriate management for patients with both IgA deficiency and celiac disease.