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Coeliac disease and autoimmune disease—genetic overlap and screening

Key Points

  • Patients with coeliac disease demonstrate concurrent autoimmune diseases more frequently (5%) than healthy individuals, and patients with autoimmune diseases often have coeliac disease, particularly those with diabetes or thyroid disease

  • Screening for coeliac disease in patients with autoimmune disease should be done regularly by evaluating serum antibodies (serological testing), although negative serology results do not entirely exclude coeliac disease

  • HLA typing offers a good negative predictive value, but only a modest positive predictive value

  • Gastroduodenoscopy whilst on gluten-containing diet is required for final diagnosis in adults, whereas HLA typing is part of the recent diagnostic work-up in children (many can be diagnosed without endoscopy)

  • Extensive genetic overlap exists between coeliac disease and other autoimmune diseases and current genetic risk profiling does not enable a precise prediction of disease development

Abstract

Coeliac disease is a treatable, gluten-induced disease that often occurs concurrently with other autoimmune diseases. In genetic studies since 2007, a partial genetic overlap between these diseases has been revealed and further insights into the pathophysiology of coeliac disease and autoimmunity have been gained. However, genetic screening is not sensitive and specific enough to accurately predict disease development. The current method to diagnose individuals with coeliac disease is serological testing for the presence of autoantibodies whilst the patient is on a regular, gluten-containing diet, followed by gastroduodenoscopy with duodenal biopsy. Serological test results can also predict the probability of coeliac disease development, even if asymptomatic. In patients with autoimmune diseases known to occur alongside coeliac disease (particularly type 1 diabetes mellitus or thyroid disorders), disease screening—and subsequent treatment if coeliac disease is detected—could have beneficial effects on progression or potential complications of both diseases, owing to the effectiveness of gluten-free dietary interventions in coeliac disease. However, whether diagnosis of coeliac disease and subsequent dietary treatment can prevent autoimmune diseases is debated. In this Review, the genetic and immunological features of coeliac disease, overlap with other autoimmune diseases and implications for current screening strategies will be discussed.

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Figure 1: Organs involved in coeliac-disease-associated autoimmunity.
Figure 2: Interpretation of genetic findings in different autoimmune diseases.

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Acknowledgements

We thank J. Senior (University of Groningen, University Medical Centre, Department of Genetics, Groningen, Netherlands) and L. M. Sollid (Centre for Immune Regulation, University of Oslo, Oslo, Norway) for carefully reading the manuscript. The work in the Wijmenga laboratory on coeliac disease is funded by the European Research Council advanced grant (FP/2007–2013/ERC grant 2012-322698). K.E.A.L. is a senior faculty member at the Centre of Immune Regulation, which is funded by the Research Council of Norway through its Centres of Excellence funding scheme, project number 179573/V40, European Research Council advanced grant (FP/2007–2013/ERC grant 2010-268541 to L. M. Sollid), South-Eastern Norway Regional Health Authority and the Norwegian ExtraFoundation for Health and Rehabilitation through EXTRA funds.

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Lundin, K., Wijmenga, C. Coeliac disease and autoimmune disease—genetic overlap and screening. Nat Rev Gastroenterol Hepatol 12, 507–515 (2015). https://doi.org/10.1038/nrgastro.2015.136

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