Poster Presentation International Celiac Disease Symposium 2026

Diagnostic accuracy of serological testing strategies for biopsy-free diagnosis of coeliac disease: an individual patient data meta-analysis   (#259)

Katie V Charlwood 1 , Ruth Brassington 1 , Efthymia Derezea 1 , Hayley E Jones 1 , Penny F Whiting 1 , Martha MC Elwenspoek 1 , CD No-Biopsy Study Group 1 , No-Biopsy Consortium 1
  1. University of Bristol, Bristol, BRISTOL, United Kingdom

Background

Recent guidance has introduced an option for diagnosis without biopsy in some children and adults with tTG-IgA levels ≥ 10x the upper limit of normal (ULN).1-3 The 10×ULN threshold was chosen as a conservative cut-off to account for heterogeneity in tTG assay performance.1 The optimal diagnostic threshold and testing strategy remain uncertain.

Methods

We conducted individual patient data meta-analysis of studies in which individuals were investigated for coeliac disease (CD) using tTG-IgA, EMA-IgA and/or DGP-IgA/IgG testing, and duodenal biopsy. Bayesian bivariate meta-analysis was used to pool the sensitivity and specificity of the serological tests individually and in combination at all possible diagnostic thresholds (1-10x ULN for tTG/DGP and positivity for EMA), using Marsh score ≥ 2 as the reference standard for diagnosis. Summary sensitivity and specificity were used to estimate positive and negative predictive values (PPV, NPV) of each test strategy at pre-test probabilities reflecting CD prevalence across different populations (1%, 5%, 10%, 35%, 50%).

Results

12,703 individuals from 23 studies were included in the analysis; 36% were diagnosed with CD. Preliminary findings suggest that tTG may have PPV ≥95% not only at a threshold of 10×ULN but also at slightly lower thresholds in higher prevalence settings. EMA specificity was found to be substantially lower than expected and showed considerable between-study heterogeneity. In adults, combining tTG and EMA may increase specificity and PPV at lower ×ULN compared with tTG alone. DGP IgG demonstrated consistently high specificity across diagnostic thresholds and may have utility in no-biopsy diagnosis.

Conclusions

These findings suggest that diagnostic strategies incorporating serological thresholds below 10×ULN may be feasible for biopsy-sparing diagnosis of coeliac disease, particularly when tests are used in combination. Ongoing analyses will explore the influence of assay technology and patient characteristics on diagnostic accuracy and the implications for refining no-biopsy diagnostic criteria.

 

  1. Husby S, Koletzko S, Korponay-Szabó I, Kurppa K, Mearin ML, Ribes-Koninckx C, et al. European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for Diagnosing Coeliac Disease 2020. J Pediatr Gastroenterol Nutr. 2020;70(1):141–56. 10.1097/mpg.0000000000002497
  2. Penny HA, Shiha MG, Raju SA, Nandi N, Trott N, Costas-Batlle C, et al. The 2026 British Society of Gastroenterology guidelines on the diagnosis and management of adult coeliac disease. Gut. 2026:gutjnl–2025–337747. 10.1136/gutjnl-2025-337747
  3. Al-Toma A, Zingone F, Branchi F, Schiepatti A, Malamut G, Canova C, 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 Gastroenterology Journal. 2025;13(10):1855–86. 10.1002/ueg2.70119