Is a general Immunoglobulin G (IgG) test reflective of tissue transglutaminase Immunoglobulin G (TTG-IgG) or is a special test required?

General IgG Testing Is Not Reflective of TTG-IgG and Requires a Special Test

A general Immunoglobulin G (IgG) test is not reflective of tissue transglutaminase IgG (TTG-IgG) antibodies and a specific test for TTG-IgG is required for celiac disease diagnosis. 1

Celiac Disease Diagnostic Testing Overview

The diagnostic approach for celiac disease involves specific serological tests:

• Primary test: IgA tissue transglutaminase antibody (tTG-IgA)

  • Sensitivity: 97.7% in children
  • Specificity: 70.2% in children 1

• Confirmatory test: IgA endomysial antibody (EMA-IgA)

  • Sensitivity: 94.5% in children
  • Specificity: 93.8% in children 1

Role of TTG-IgG Testing

TTG-IgG testing is only indicated in specific circumstances:

• When IgA deficiency is present (occurs in 2-3% of celiac patients) 1
• When tTG-IgA results are negative but clinical suspicion remains high 2

The American Diabetes Association and Diabetes Care guidelines specifically recommend:

• "Screen children with type 1 diabetes for celiac disease by measuring IgA tissue transglutaminase (tTG) antibodies, with documentation of normal total serum IgA levels, or IgG to tTG and deamidated gliadin antibodies if IgA deficient." 2

Important Distinctions Between General IgG and TTG-IgG

1. Different targets:

   • General IgG measures overall immunoglobulin G levels in blood
   • TTG-IgG specifically measures antibodies targeting tissue transglutaminase

2. Clinical utility:

   • General IgG has no diagnostic value for celiac disease
   • TTG-IgG has limited utility (only 3% diagnostic yield when used alone) 3

3. Test methodology:

   • TTG-IgG requires specific ELISA testing methodology targeting tissue transglutaminase 4, 5

Clinical Implications

• TTG-IgG testing should not be used as a primary screening test for celiac disease 3
• When TTG-IgA is negative, an isolated positive TTG-IgG has very low utility (3%) in diagnosing celiac disease 3
• Total serum IgA levels should be measured alongside TTG-IgA to rule out IgA deficiency 2, 1

Pitfalls to Avoid

• Do not rely on general IgG testing for celiac disease diagnosis
• Do not use TTG-IgG as a first-line test in patients with normal IgA levels
• Do not interpret an isolated positive TTG-IgG (with negative TTG-IgA) as diagnostic of celiac disease without further investigation
• Do not perform celiac testing in patients already on a gluten-free diet (false negatives likely) 1

For accurate celiac disease diagnosis, specific serological tests (TTG-IgA, EMA-IgA) must be ordered, and in cases of IgA deficiency, specific TTG-IgG testing is required rather than general IgG measurement.