The Role of Anti-tTG IgA Test in Diagnosing Coeliac Disease
The IgA anti-tissue transglutaminase (tTG-IgA) test is the preferred initial screening test for coeliac disease due to its high sensitivity (90-96%) and specificity (>95%), and should be performed while the patient is on a gluten-containing diet. 1
Initial Diagnostic Testing
- tTG-IgA is the most efficient single serologic test for detecting coeliac disease in the primary care setting 2
- Testing must be performed while the patient is on a gluten-containing diet (at least 10g daily for 6-8 weeks) to avoid false negative results 1
- The test has excellent sensitivity (90-96%) and specificity (>95%), making it superior to older gliadin antibody testing 2, 1
- Total IgA levels should be measured when there is suspicion of IgA deficiency, as this could lead to false negative results 1, 3
Confirmatory Testing
- Positive serologic results should be followed by intestinal biopsy, which remains the gold standard for diagnosis 2
- Multiple duodenal biopsy specimens (ideally 6) should be taken from the second part of the duodenum or beyond 2, 1
- Characteristic histologic findings include villous atrophy, crypt lengthening, and increased intraepithelial lymphocytes 2, 1
- In patients with tTG-IgA levels >10x upper limit of normal, IgA endomysial antibody (EMA-IgA) should be performed as a confirmatory test due to its excellent specificity (99.6%) 1, 3
Special Testing Considerations
- In IgA-deficient patients, IgG-based tests should be used instead:
- IgG anti-tTG testing has limited utility when tTG-IgA is negative in patients with normal IgA levels 5
- The combination of tTG-IgA and EMA-IgA has a positive predictive value approaching 97% 6
- HLA-DQ2 and HLA-DQ8 testing has high negative predictive value and is useful when coeliac disease is strongly suspected despite negative serology 1, 7
High-Risk Groups to Consider Testing
- First-degree relatives of patients with coeliac disease 1, 7
- Patients with type 1 diabetes mellitus 1, 7
- Patients with unexplained iron deficiency anemia 1, 7
- Patients with premature osteoporosis 1, 7
- Patients with autoimmune thyroid disease 1
- Patients with unexplained liver transaminase elevations 1, 7
- Patients with Down syndrome 1, 7
Common Pitfalls in Diagnosis
- Initiating a gluten-free diet before completing diagnostic testing can lead to false-negative results 1, 3
- Relying solely on serology without biopsy confirmation can lead to misdiagnosis 2, 1
- IgG isotype testing for tTG antibody has limited utility in the absence of IgA deficiency 5
- Antigliadin antibody testing is outdated and should not be used as the primary test due to inferior diagnostic performance 2
- In children under 2 years, tTG-IgA testing should be combined with IgG and IgA deamidated gliadin peptides for improved sensitivity 2, 7