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Diagnosing coeliac disease and the potential for serological markers

Nature Reviews Gastroenterology & Hepatology volume 11, pages 655–663 (2014)Cite this article

Subjects

Key Points

  • Coeliac disease presents in many different ways at any age

  • All initial testing, except HLA genotyping, should be done whilst patients are on a gluten-containing diet

  • Coeliac-specific serological tests have improved and now rival the accuracy of biopsy results in many circumstances

  • Duodenal biopsies can be avoided in a minority of patients when specific serological, HLA and clinical criteria are met

  • The negative predictive value of HLA genotype risk determination is a useful adjunct to coeliac disease diagnosis, especially in those already on a gluten-free diet

  • Biopsies remain an important part of the diagnosis for coeliac disease in the majority of patients

Abstract

The diagnosis of coeliac disease has advanced in the past decade owing to increased clinical awareness and improved tests. Coeliac disease is now regarded as a common disease presenting at any age with a broad spectrum of symptoms. Previous guidelines on diagnosis relied on the histological analysis of duodenal biopsy samples. However, contemporary antibody analysis is a diagnostic tool with a comparatively high accuracy that has reduced reliance on performing biopsies. Furthermore, determination of HLA-based genetic susceptibility to coeliac disease has become routine. European and North American guidelines utilize symptoms, coeliac antibodies (primarily tissue transglutaminase 2 IgA and endomysial IgA antibodies), HLA determination and histological analysis of biopsy tissue for diagnosis. Some guidelines conclude that the diagnostic accuracy of tissue transglutaminase 2 IgA antibodies is sufficient to omit duodenal biopsies in selected children with very high antibody levels, in the presence of clear symptom response as well as a positive endomysial antibody test and confirmation of genetic susceptibility. This Review discusses if such a strategy is appropriate for children and adults in all populations. The performance characteristics of antibody tests (particularly of the tissue transglutaminase 2 IgA test) including quality control and characterisation of the population in whom testing is performed are also discussed.

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Figure 1: Clinical patterns of coeliac disease.
Figure 2: Histological features of coeliac disease.
Figure 3: Increasing titres of coeliac-disease-specific antibodies, specifically tTG2 IgA correlates with increasing certainty of the presence of coeliac disease.

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  1. Hans Christian Andersen Children's Hospital, Odense University Hospital, 29 Southern Boulevard, DK-5000, Odense C, Denmark

    Steffen Husby

  2. Division of Gastroenterology and Hepatology, Mayo Clinic, 200 1st Street South West, Rochester, 55905, MN, USA

    Joseph A. Murray

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S.H. and J.A.M. contributed equally to this manuscript.

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J.A.M. declares the following support and associations: grant support from Alba Therapeutics, Alvine Pharmaceuticals, Inc. Member of the advisory board for Alvine Pharmaceuticals Inc. and is a consultant for AMAG Pharmaceuticals, Entera Health Inc., Sonomaceuticals LLC, BioLineRx and GlaxoSmithKline. S.H. declares no competing interests.

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Husby, S., Murray, J. Diagnosing coeliac disease and the potential for serological markers. Nat Rev Gastroenterol Hepatol 11, 655–663 (2014). https://doi.org/10.1038/nrgastro.2014.162

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