How to interpret positive anti-Tissue Transglutaminase (anti-TTG) Immunoglobulin A (IgA) and total IgA results in patients with suspected celiac disease?

From the Guidelines

Interpreting positive anti-Tissue Transglutaminase (anti-TTG) IgA and total IgA results requires careful consideration of both values together, with a positive anti-TTG IgA result suggesting celiac disease, especially in the context of normal total IgA levels and values exceeding 10 times the upper limit of normal, as indicated by recent guidelines 1. When a patient has elevated anti-TTG IgA levels along with normal total IgA levels, this strongly suggests celiac disease. The total IgA measurement is crucial because approximately 2-3% of celiac patients have IgA deficiency, which could lead to false-negative anti-TTG IgA results.

• Key considerations in interpretation include:
  • The level of anti-TTG IgA, with higher levels more strongly suggesting celiac disease
  • The total IgA level, to assess for IgA deficiency
  • Clinical symptoms and histological findings, such as villous atrophy, which support the diagnosis of celiac disease In cases of IgA deficiency, additional testing with IgG-based antibodies (anti-TTG IgG or anti-deamidated gliadin peptide IgG) should be performed, as suggested by guidelines 1.
• The use of these tests in monitoring disease management and dietary compliance is also important, with declining antibody levels indicating adherence to a gluten-free diet, as noted in recent studies 1. Even with positive serological results, a definitive diagnosis typically requires duodenal biopsies showing characteristic intestinal damage while the patient is on a gluten-containing diet.
• The height of anti-TTG IgA titers often correlates with the severity of intestinal damage, though some guidelines now suggest that very high antibody levels (>10x upper limit) in symptomatic children may be sufficient for diagnosis without biopsy, highlighting the importance of considering clinical context and recent evidence 1. After diagnosis and implementation of a strict gluten-free diet, antibody levels should gradually decrease, making these tests useful for monitoring dietary compliance and disease management.
• Ongoing assessment and management should be guided by the most recent and highest quality evidence, prioritizing patient outcomes in terms of morbidity, mortality, and quality of life, as emphasized in current clinical practice updates 1.

From the Research

Interpreting Anti-TTG IgA and Total IgA Results

To interpret positive anti-Tissue Transglutaminase (anti-TTG) Immunoglobulin A (IgA) and total IgA results in patients with suspected celiac disease, consider the following points:

• The presence of anti-TTG IgA antibodies is a sensitive indicator of celiac disease, but it is essential to also measure total IgA to rule out IgA deficiency, which can lead to false-negative results 2.
• A positive anti-TTG IgA result with a normal total IgA level is indicative of celiac disease, while a positive result with a low total IgA level may require further evaluation to confirm the diagnosis 2.
• The utility of isolated positive tTG IgG in diagnosing celiac disease is low, and it is recommended to measure both tTG IgA and tTG IgG or total IgA to increase the diagnostic accuracy 2.

Factors Influencing Interpretation

Several factors can influence the interpretation of anti-TTG IgA and total IgA results, including:

• The type of assay used, as different assays can have varying levels of sensitivity and specificity 3, 4.
• The patient's clinical presentation, as those with gastrointestinal symptoms or iron deficiency anemia may be more likely to have celiac disease 2.
• The patient's age, as children diagnosed before the age of two years may have lower autoantibody titers 5.
• The presence of other autoimmune disorders or conditions that can affect the results, such as HLA-DR7 positivity 5.

Clinical Implications

The interpretation of anti-TTG IgA and total IgA results has significant clinical implications, including:

• The need for further evaluation, such as intestinal biopsy, to confirm the diagnosis of celiac disease 2, 6.
• The importance of monitoring patients on a gluten-free diet to assess their response to treatment and adjust their management plan as needed 5, 3.
• The potential for false-negative or false-positive results, which can lead to misdiagnosis or delayed diagnosis, highlighting the need for careful interpretation of results in the context of clinical presentation and other diagnostic findings 4.