Published: July 2026
Medically reviewed by:
Mercè Tena Campos, Scientific Affairs Manager
Evidence supporting streamlined serologic testing strategies in patients with positive anti-tTG IgA results
Celiac disease (CD) is a chronic immune-mediated enteropathy in which accurate and timely diagnosis is essential to reduce the risk of long-term complications.1 Tissue transglutaminase IgA antibodies (tTG-IgA) are widely recognized as the primary serologic marker for CD due to their high diagnostic performance.2–4
While some diagnostic guidelines continue to recommend EMA testing as a confirmatory test,2–4 particularly in borderline cases, emerging evidence suggests that EMA may provide limited additional diagnostic value when tTG-IgA results are already positive.5–7
Clinical practice should continue to follow applicable regional guidelines and local standards of care.
A recent study published in Frontline Gastroenterology evaluated the clinical utility of EMA testing alongside tTG-IgA and reported limited incremental diagnostic benefit from EMA testing in both borderline and positive tTG-IgA cohorts.8
Key findings from Yau et al., Frontline Gastroenterology (2026)
Retrospective cohort of 554 CD patients and 33 non-CD patients tested for both tTG-IgA and EMA, before diagnosis:8
- EMA demonstrated low sensitivity and specificity in patients with borderline EliA™ Celikey tTG-IgA test results (7–10 EliA U/ml).
- No statistically significant association was observed between EMA status and biopsy-confirmed celiac disease in the borderline cohort (p=0.7341).
- Among patients with positive tTG-IgA (>10 EliA U/ml), EMA added minimal clinical utility due to high concordance with tTG positivity.
- 61% (14/23) of EMA-negative patients with positive tTG-IgA still had confirmed celiac disease.
- Authors concluded that routine EMA testing may not improve diagnostic decision-making when tTG-IgA is already positive.
“EMA had low sensitivity in borderline cases and added no diagnostic value when tTG was positive.”
Tissue transglutaminase IgA antibodies remain the cornerstone serologic marker for CD
Multiple international studies and guideline reviews support the high diagnostic performance of anti-tTG IgA assays in celiac disease diagnosis EMA.
Evidence supporting tTG-IgA testing includes:
- High sensitivity across pediatric and adult populations.1–3
- Strong predictive value at elevated titers.5,6,9,10
- Support for no-biopsy diagnostic approaches in selected patient populations.3,6,10,11
- Objective, commercially standardized assay formats suitable for routine and high-throughput laboratory testing.5,9
- At high titer, concordance between tTG-IgA and EMA is high, reported as >98%.5,11,12
The study by Yau et al. further reinforces prior evidence suggesting that EMA testing may offer limited incremental benefit when robust tTG-IgA testing is already available.8
Operational considerations of EMA testing
EMA testing has historically been considered highly specific for celiac disease; however, practical and analytical limitations have been reported.
Published limitations of EMA testing include:
- Requirement for specialized expertise2,5,9
- Interobserver variability1,6,9
- Labor-intensive / lower workflow automation compared with FEIA-based tTG assays3,9
- Costly, requires specialized tissue substrate2,9
Yau et al. additionally noted that many laboratories have reduced or discontinued routine EMA testing because of workflow complexity and limited incremental diagnostic value.8
Automated EliA celiac disease testing solutions
The EliA celiac disease portfolio on Phadia Laboratory Systems supports standardized, automated serologic testing workflows for celiac disease diagnostics.
Available assays include:
- EliA™ Celikey IgA assay
- EliA™ Celikey IgG assay
- EliA™ GliadinDP IgA assay
- EliA™ GliadinDP IgG assay
Features of EliA FEIA assays include:
- Automated processing
- Objective quantitative results
- Wide range of instruments and capacities
- Integration across Phadia™ Laboratory Systems
The EliA Celikey IgA assay uses human recombinant tissue transglutaminase antigen and defines:13
- Negative: <7 EliA U/ml
- Equivocal: 7–10 EliA U/ml
- Positive: >10 EliA U/ml
Supporting evidence-based diagnostic pathways
As celiac disease diagnostic strategies continue to evolve, emerging evidence supports the value of streamlined serologic workflows centered on high quality anti-tTG IgA testing.3,9
Recent evidence from Yau et al. contributes to the growing body of literature evaluating the incremental clinical utility of EMA testing in patients with positive tTG-IgA results.8
Thermo Fisher Scientific remains committed to supporting laboratories with evidence-based, standardized testing solutions that support CD diagnosis while aligning with regional guidelines and standards of care.
