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Evidence supporting safe diagnosis of coeliac disease in children with antitissue transglutaminase titre ≥5 times upper limit of normal
  1. Siba Prosad Paul1,2,
  2. Daniyal Isam Raja1,3,
  3. Bhupinder Kaur Sandhu1,
  4. Srinivasa R Rao4,
  5. Christine H Spray1,
  6. Anthony Edward Wiskin1,
  7. Lakshmipriya Selvarajan1,
  8. Eleni Volonaki1,
  9. Pramila Ramani5,
  10. Lina Bourhan Tashtoush1,
  11. Dharamveer Basude1
  1. 1 Paediatric Gastroenterology, Bristol Royal Hospital for Children, Bristol, UK
  2. 2 Paediatrics, Yeovil District Hospital, Yeovil, UK
  3. 3 Medical School, University of Exeter, Exeter, Devon, UK
  4. 4 Nuffield Department of Surgical Sciences, University of Oxford, Oxford, Oxfordshire, UK
  5. 5 Paediatric Histopathology, Bristol Royal Hospital for Children, Bristol, UK
  1. Correspondence to Dr Siba Prosad Paul, Paediatric Gastroenterology, Bristol Royal Hospital for Children, Bristol, BS2 8BJ, UK; siba.paul{at}


Objective European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines on coeliac disease (CD) recommend that children who have IgA-based antitissue transglutaminase (TGA-IgA) titre ≥10× upper limit of normal (ULN) and positive antiendomysial antibody, can be reliably diagnosed with CD via the no-biopsy pathway. The aim of this study was to examine the relationship between TGA-IgA ≥5×ULN and histologically confirmed diagnosis of CD.

Methods Data including TGA-IgA levels at upper gastrointestinal endoscopy and histological findings from children diagnosed with CD following endoscopy from 2006 to 2021 were analysed. CD was confirmed by Marsh-Oberhuber histological grading 2 to 3 c. Statistical analysis was performed using χ² analysis (p<0.05= significant).

Results 722 of 758 children had histological confirmation of CD. 457 children had TGA-IgA ≥5×ULN and 455 (99.5%) of these had histological confirmation for CD; the two that did not had eventual diagnosis of CD based on clinicopathological features. 114 of 457 had between TGA-IgA ≥5×ULN and <10×ULN, all had confirmed CD. The likelihood of a positive biopsy with TGA-IgA ≥5×ULN (455/457) compared with TGA-IgA <5×ULN (267/301) has strong statistical significance (p<0.00001). The optimal TGA-IgA cut-off from receiver operating characteristic curve analysis was determined to be below 5×ULN for the two assays used.

Conclusion 99.5% of children with TGA-IgA ≥5×ULN had histological confirmation of CD, suggesting that CD diagnosis can be made securely in children with TGA-IgA ≥5×ULN. If other studies confirm this finding, there is a case to be made to modify the ESPGHAN guidelines to a lower threshold of TGA-IgA for serological diagnosis of CD.

  • gastroenterology
  • pathology

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  • Contributors SPP, DB and BKS: project concept, supervision, prepared and edited the manuscript with comments and review from all authors. SPP, DIR, LBT and DB: generation of patient list through endoscopy register search, collected and analysed data. SRR: data analysis and statistical calculation. CHS, AEW, EV, LS and PR: provided advisory input and helped in editing the manuscript. BKS: guarantor for the study. All authors have approved the uploaded draft.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.