Recommended Initial Blood Test for Celiac Disease
The tissue transglutaminase IgA (tTG-IgA) antibody test combined with total IgA level measurement is the recommended first-line blood test for suspected celiac disease. 1, 2
Primary Serologic Testing Strategy
tTG-IgA serves as the preferred initial screening test with sensitivity of 90.7% and specificity of 87.4% in adults, and even higher sensitivity of 97.7% in children 1, 2
Total IgA level must be measured simultaneously to identify IgA deficiency, which occurs in 1-3% of celiac disease patients and causes falsely negative IgA-based test results 1, 2, 3
The combination of these two tests ensures that IgA-deficient patients are not missed, as they would have falsely negative tTG-IgA results despite having active celiac disease 4
Confirmatory Testing When Initial Screen is Positive
Endomysial antibody (EMA) IgA should be performed as confirmatory testing when tTG-IgA is elevated, offering excellent specificity of 99.6% in adults and 93.8% in children 1, 2
When tTG-IgA exceeds 10 times the upper limit of normal combined with positive EMA in a second blood sample, the positive predictive value for celiac disease approaches 100% 1, 3
This dual-positive result (high tTG-IgA plus positive EMA) provides virtual diagnostic certainty and justifies proceeding directly to endoscopy for biopsy confirmation 1, 3
Alternative Testing for IgA-Deficient Patients
If IgA deficiency is confirmed, switch to IgG-based testing using IgG deamidated gliadin peptide (DGP-IgG), which has superior diagnostic accuracy (93.6% sensitivity, 99.4% specificity) compared to tTG-IgG 2
IgG endomysial antibodies and IgG tissue transglutaminase antibodies are also useful for identifying IgA-deficient patients with celiac disease 4
IgG tTG alone has limited utility with sensitivity ranging only 40.6-84.6%, making it less reliable than DGP-IgG in IgA-deficient patients 2
Critical Pre-Testing Requirements
The patient must be consuming adequate gluten (at least 10g daily, equivalent to approximately 3 slices of wheat bread) for 6-8 weeks prior to testing to avoid false-negative results 1, 3, 5
Reduction or avoidance of gluten before diagnostic testing significantly reduces the sensitivity of both serology and biopsy testing 1
If a patient has already reduced gluten intake, they should resume a normal gluten-containing diet for 1-3 months before testing 1
Common Pitfalls to Avoid
Never rely on IgG-based tests as first-line screening in patients with normal IgA levels, as IgG isotype testing for tTG antibody is not specific in the absence of IgA deficiency 1
Do not start a gluten-free diet before completing the diagnostic workup, as this leads to false-negative serology and inconclusive biopsies 1, 3
Avoid ordering only tTG-IgA without total IgA level, as this misses the 1-3% of celiac patients who are IgA-deficient 1, 2, 3
Algorithmic Approach to Initial Testing
Order tTG-IgA plus total IgA level as the initial screening test 1, 2
If tTG-IgA is positive and total IgA is normal: Order confirmatory EMA-IgA testing 1, 2
If tTG-IgA is negative but total IgA is low/absent: Order IgG-based tests (DGP-IgG preferred) 2, 4
If both tTG-IgA and EMA are positive: Proceed to upper endoscopy with duodenal biopsies (at least 6 specimens) for definitive diagnosis 1, 3
If serology is negative but clinical suspicion remains high: Consider HLA-DQ2/DQ8 testing (negative predictive value >99%) or proceed directly to endoscopy 1, 2
Performance Characteristics in Clinical Context
The tTG-IgA test performs better at ruling out celiac disease than ruling it in, due to specificity being lower than sensitivity in some populations 2
In untreated celiac disease, the concordance rate between EMA and tTG-IgA approaches 100%, providing strong diagnostic confidence when both are positive 6, 7
False-positive tTG results can occur in patients with chronic infections, inflammatory bowel disease, liver disease, or other autoimmune conditions, making confirmatory EMA testing essential 2