Why TTG and IgA Are Both Sent for Celiac Disease Workup
Total IgA levels must be measured simultaneously with TTG-IgA because approximately 1-3% of celiac disease patients have selective IgA deficiency, which causes falsely negative TTG-IgA results and would lead to missed diagnoses. 1, 2
The Critical Role of IgA Measurement
The primary reason for checking total IgA alongside TTG-IgA is to identify patients with IgA deficiency, which would render the TTG-IgA test unreliable:
- IgA deficiency occurs 10-15 times more frequently in celiac disease patients compared to the general population 2
- When IgA is deficient, the TTG-IgA test will be falsely negative regardless of whether active celiac disease is present 1
- Without measuring total IgA, you cannot interpret a negative TTG-IgA result with confidence 2
The Algorithmic Approach
When Total IgA is Normal:
- A positive TTG-IgA has excellent diagnostic accuracy (sensitivity 90-96%, specificity >95%) 1, 2
- A negative TTG-IgA effectively rules out celiac disease in most cases 3
- Proceed with standard diagnostic pathway based on TTG-IgA results 1
When IgA Deficiency is Detected:
- Switch to IgG-based testing immediately - specifically IgG deamidated gliadin peptide (DGP-IgG), which has superior accuracy (93.6% sensitivity, 99.4% specificity) compared to TTG-IgG 1, 3
- IgG TTG has poor performance characteristics (sensitivity only 40.6-84.6%) and should not be relied upon 3
- The original TTG-IgA result must be disregarded as unreliable 1
Common Clinical Pitfall
The most critical error is ordering TTG-IgA alone without total IgA. This creates an uninterpretable result when TTG-IgA is negative, because you cannot distinguish between:
In this scenario, if clinical suspicion remains high, you must either:
- Measure total IgA retrospectively and potentially retest with IgG-based assays 1
- Proceed directly to endoscopy with duodenal biopsy 1
Alternative Approach (Not Routinely Recommended)
While the American Gastroenterological Association states that routine measurement of total IgA is "not warranted as a first step" unless IgA deficiency is strongly suspected, current best practice favors simultaneous testing to avoid the diagnostic dilemma of an uninterpretable negative TTG-IgA 1, 2. The guideline suggests measuring IgA as "an appropriate next step" only after a negative TTG-IgA when suspicion remains high, but this sequential approach delays diagnosis and requires additional patient visits 1.
Practical Implementation
- Order both tests together initially - this is the most efficient workflow 2
- Some newer chemiluminescent assays can identify IgA deficiency using TTG relative light units <300, potentially eliminating the need for separate total IgA testing 4
- If total IgA is normal, the TTG-IgA result stands alone as highly reliable 1, 2