Thermo Fisher – The Emerging Role of EMA in Celiac Disease Diagnosis

The diagnosis of celiac disease has evolved considerably over the past decade, driven by advances in serological testing and a growing body of clinical evidence.

While endomysial antibody (EMA) testing has historically served as a confirmatory test alongside tissue transglutaminase IgA (tTG-IgA) testing, emerging research suggests its role may be more limited than previously thought in patients who already have positive tTG-IgA results.²˒⁴⁻⁸

A recent study by Yau A and colleagues, published in Frontline Gastroenterology in 2026, provides further evidence supporting streamlined serological testing pathways that prioritise high-quality tTG-IgA assays for the diagnosis of celiac disease.⁸

Why Early and Accurate Diagnosis Matters

Celiac disease is a chronic, immune-mediated disorder triggered by dietary gluten in genetically susceptible individuals. Undiagnosed or delayed diagnosis can lead to long-term complications, including malabsorption, nutritional deficiencies, osteoporosis, infertility, and an increased risk of certain malignancies.¹

As a result, diagnostic accuracy and efficiency remain critical priorities for clinicians and laboratories alike.¹⁻⁴

The Historical Role of EMA Testing

For many years, EMA testing has been regarded as a highly specific marker for celiac disease and has often been incorporated into diagnostic algorithms as a confirmatory test, particularly when tTG-IgA results are borderline or equivocal. Several regional guidelines continue to include EMA testing as part of the diagnostic process.²˒⁴˒⁵

However, EMA testing presents several practical challenges:

• It requires specialised technical expertise.²˒⁵˒⁹
• Results can be subject to inter-observer variability.¹˒⁶˒⁹
• The testing process is labour-intensive and less suited to automation.³˒⁹
• It requires specialised tissue substrates, which contribute to higher operational costs.²˒⁹

These limitations have prompted many laboratories to reassess the routine use of EMA testing in modern diagnostic workflows.⁸˒⁹

What the Latest Evidence Shows

The study by Yau A et al. evaluated 554 patients with celiac disease and 33 without, all of whom underwent both tTG-IgA and EMA testing before diagnosis. The findings raise important questions about the incremental value of EMA testing when reliable tTG-IgA results are already available.⁸

Key observations included:

• EMA showed low sensitivity and specificity in patients with borderline EliA™ Celikey tTG-IgA results (7-10 EliA U/mL).⁸
• No statistically significant association was found between EMA status and biopsy-confirmed celiac disease in the borderline cohort (p=0.7341).⁸
• Among patients with positive tTG-IgA results (>10 EliA U/mL), EMA provided minimal additional clinical utility because of the high concordance between the two assays.⁸
• Notably, 61% of EMA-negative patients with positive tTG-IgA results still had confirmed celiac disease.⁸

The authors concluded that routine EMA testing may not improve diagnostic decision-making when tTG-IgA is already positive.⁸

Why tTG-IgA Remains the Cornerstone of Celiac Disease Testing

A growing body of international evidence continues to support tTG-IgA as the primary serological marker for diagnosing celiac disease. Studies and guideline reviews have consistently demonstrated:¹⁻³˒⁵˒⁶˒⁹˒¹⁰

• High diagnostic sensitivity across paediatric and adult populations.¹⁻³
• Strong predictive value at elevated antibody titres.⁵˒⁶˒⁹˒¹⁰
• Support for no-biopsy diagnostic pathways in selected patient populations.³˒⁶˒¹⁰˒¹¹
• Objective, standardised assay formats suitable for routine laboratory workflows.⁵˒⁹
• Greater than 98% concordance between tTG-IgA and EMA at higher antibody titres.⁵˒¹¹˒¹²

These advantages make modern tTG-IgA testing particularly attractive for laboratories seeking diagnostic confidence alongside operational efficiency.³˒⁵˒⁹

Implications for Clinical Laboratories

As healthcare systems continue to focus on efficiency, standardisation, and evidence-based practice, diagnostic workflows are increasingly being reviewed to reduce unnecessary testing without compromising patient care.³˒⁹

The findings from Yau A et al. contribute to a growing discussion about whether routine EMA testing remains necessary when robust, validated tTG-IgA testing platforms are already in place.⁸

While laboratories should always follow regional guidelines and local standards of care, the latest evidence suggests that streamlined serological strategies centred on high-quality tTG-IgA testing may support both diagnostic accuracy and laboratory efficiency.³˒⁸˒⁹

Supporting Evidence-Based Celiac Disease Pathways

The Thermo Fisher Scientific EliA™ celiac disease testing portfolio supports standardised, automated serological testing workflows, including the EliA™ Celikey IgA assay, which uses a recombinant human tissue transglutaminase antigen and delivers objective, quantitative results suitable for laboratories of varying sizes.¹³

As the evidence base continues to evolve, laboratories have an opportunity to review their testing strategies and ensure diagnostic pathways remain aligned with current clinical evidence and operational best practice.³˒⁸˒⁹

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Reference List

1. Sheppard AL, et al. Systematic review with meta-analysis: the accuracy of serological tests to support the diagnosis of coeliac disease. Aliment Pharmacol Ther. 2022;55(5):514-527
2. Husby S, et al. European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for Diagnosing Coeliac Disease 2020. J Pediatr Gastroenterol Nutr. 2020;70(1):141-156.
3. Al-Toma A, et al. European Society for the Study of Coeliac Disease 2025 Updated Guidelines on the Diagnosis and Management of Coeliac Disease in Adults. Part 1: Diagnostic Approach. United European Gastroenterol J. 2025;13(10):1855-1886.
4. Rubio-Tapia A, et al. American College of Gastroenterology Guidelines Update: Diagnosis and Management of Celiac Disease. Am J Gastroenterol. 2023;118(1):59-76.
5. Ben-Tov A, et al. Endomysial antibodies or anti-tissue transglutaminase type 2 IgA antibodies as a confirmatory test in children with celiac disease. J Pediatr Gastroenterol Nutr. 2025;80(1):147-150.
6. Ciacci C, et al. Serum anti-tissue transglutaminase IgA and prediction of duodenal villous atrophy in adults with suspected coeliac disease without IgA deficiency (Bi.A.CeD). Lancet Gastroenterol Hepatol. 2023;8(11):1005-1014.
7. Brown SD, et al. Is there utility in testing IgA-endomysial antibodies in patients with weak-positive or equivocal IgA-tissue transglutaminase antibodies in the diagnosis of coeliac disease? Ann Clin Biochem. 2026;63(1):32-39.
8. Yau A, et al. Anti-endomysial antibody detection is of no benefit as an adjunct to IgA anti-tissue transglutaminase antibodies in the serological diagnosis of coeliac disease. Frontline Gastroenterol. 2026;17:e103344.
9. Penny HA, et al. Progress in the serology-based diagnosis and management of adult celiac disease. Expert Rev Gastroenterol Hepatol. 2020;14(3):147-154.
10. Penny HA, et al. Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts. Gut. 2021;70(5):876-883.
11. Werkstetter KJ, et al. Accuracy in Diagnosis of Celiac Disease Without Biopsies in Clinical Practice. Gastroenterology. 2017;153(4):924-935.
12. Ezra S, et al. Analysis of Anti-Tissue Transglutaminase and Anti-Endomysial Antibody Discordance in a Celiac Disease Screening Serology Testing Algorithm. Clin Chem. 2023;69(Suppl 1):hvad097.402.

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