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Systematic review with meta-analysis: the accuracy of serological tests to support the diagnosis of coeliac disease

Systematic review with meta-analysis: the accuracy of serological tests to support the diagnosis of coeliac disease
Systematic review with meta-analysis: the accuracy of serological tests to support the diagnosis of coeliac disease

Background: There is growing support for a biopsy avoidant approach to diagnose coeliac disease in both children and adults, using a serological diagnosis instead. Aims: To assess the diagnostic accuracy of serological tests for coeliac disease in adults and children. Methods: Seven electronic databases were searched between January 1990 and August 2020. Eligible diagnostic studies evaluated the accuracy of serological tests for coeliac disease against duodenal biopsy. Risk of bias assessment was performed using QUADAS-2. Bivariate random-effects meta-analyses were used to estimate serology sensitivity and specificity at the most commonly reported thresholds. Results: 113 studies (n = 28,338) were included, all in secondary care populations. A subset of studies were included in meta-analyses due to variations in diagnostic thresholds. Summary sensitivity and specificity of immunoglobulin A (IgA) anti-tissue transglutaminase were 90.7% (95% confidence interval: 87.3%, 93.2%) and 87.4% (84.4%, 90.0%) in adults (5 studies) and 97.7% (91.0%, 99.4%) and 70.2% (39.3%, 89.6%) in children (6 studies); and of IgA endomysial antibodies were 88.0% (75.2%, 94.7%) and 99.6% (92.3%, 100%) in adults (5 studies) and 94.5% (88.9%, 97.3%) and 93.8% (85.2%, 97.5%) in children (5 studies). Conclusions: Anti-tissue transglutaminase sensitivity appears to be sufficient to rule out coeliac disease in children. The high specificity of endomysial antibody in adults supports its use to rule in coeliac disease. This evidence underpins the current development of clinical guidelines for a serological diagnosis of coeliac disease. Studies in primary care are needed to evaluate serological testing strategies in this setting.

coeliac disease, diagnostic tests, meta-analyses
0269-2813
514-527
Sheppard, Athena
c3f0ab18-23ee-422a-af58-ea377a30000d
Elwenspoek, Martha M.C.
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Scott, Lauren J.
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Corfield, Victoria
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Everitt, Hazel
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Gillett, Peter M.
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Hay, Alastair D.
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Jones, Hayley E.
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Mallett, Susan
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Watson, Jessica
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Whiting, Penny F.
a30d75d5-8b68-4625-a166-1e71443a0b4f
Sheppard, Athena
c3f0ab18-23ee-422a-af58-ea377a30000d
Elwenspoek, Martha M.C.
6fa131b1-b60f-4eb8-a6cb-f3dab87b845c
Scott, Lauren J.
6716aa49-970c-4bf8-a4e4-fab7cf7dc62e
Corfield, Victoria
65a698f1-9cb8-43ee-ad4d-64f64793d0f3
Everitt, Hazel
80b9452f-9632-45a8-b017-ceeeee6971ef
Gillett, Peter M.
f7dce00d-6363-4d99-a80a-d931cb35a631
Hay, Alastair D.
bfae9e44-ae9b-473c-923f-1dea50747023
Jones, Hayley E.
22849f0d-6153-40f9-87a9-8a62f6d3b045
Mallett, Susan
9f55a45b-6330-45e9-b817-2f69ebe32d5d
Watson, Jessica
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Whiting, Penny F.
a30d75d5-8b68-4625-a166-1e71443a0b4f

Sheppard, Athena, Elwenspoek, Martha M.C., Scott, Lauren J., Corfield, Victoria, Everitt, Hazel, Gillett, Peter M., Hay, Alastair D., Jones, Hayley E., Mallett, Susan, Watson, Jessica and Whiting, Penny F. (2022) Systematic review with meta-analysis: the accuracy of serological tests to support the diagnosis of coeliac disease. Alimentary Pharmacology and Therapeutics, 55 (5), 514-527. (doi:10.1111/apt.16729).

Record type: Review

Abstract

Background: There is growing support for a biopsy avoidant approach to diagnose coeliac disease in both children and adults, using a serological diagnosis instead. Aims: To assess the diagnostic accuracy of serological tests for coeliac disease in adults and children. Methods: Seven electronic databases were searched between January 1990 and August 2020. Eligible diagnostic studies evaluated the accuracy of serological tests for coeliac disease against duodenal biopsy. Risk of bias assessment was performed using QUADAS-2. Bivariate random-effects meta-analyses were used to estimate serology sensitivity and specificity at the most commonly reported thresholds. Results: 113 studies (n = 28,338) were included, all in secondary care populations. A subset of studies were included in meta-analyses due to variations in diagnostic thresholds. Summary sensitivity and specificity of immunoglobulin A (IgA) anti-tissue transglutaminase were 90.7% (95% confidence interval: 87.3%, 93.2%) and 87.4% (84.4%, 90.0%) in adults (5 studies) and 97.7% (91.0%, 99.4%) and 70.2% (39.3%, 89.6%) in children (6 studies); and of IgA endomysial antibodies were 88.0% (75.2%, 94.7%) and 99.6% (92.3%, 100%) in adults (5 studies) and 94.5% (88.9%, 97.3%) and 93.8% (85.2%, 97.5%) in children (5 studies). Conclusions: Anti-tissue transglutaminase sensitivity appears to be sufficient to rule out coeliac disease in children. The high specificity of endomysial antibody in adults supports its use to rule in coeliac disease. This evidence underpins the current development of clinical guidelines for a serological diagnosis of coeliac disease. Studies in primary care are needed to evaluate serological testing strategies in this setting.

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Accepted/In Press date: 28 November 2021
Published date: March 2022
Additional Information: Funding Information: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment Programme (grant number NIHR129020). Athena L. Sheppard (Systematic Review Fellowship, grant number NIHR‐RM‐SR‐2017‐08‐012) was funded by the NIHR for this research project. This research was supported by the NIHR Applied Research Collaboration West (NIHR ARC West) at University Hospital Bristol NHS Foundation Trust. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Declaration of funding interests: Funding Information: Declaration of personal interests: Athena L. Sheppard has received research funding from the National Institute for Health Research. The authors wish to thank Alison Richards, Research Associate, and Sarah Dawson, Senior Research Associate in Information Retrieval, at NIHR ARC West at University Hospitals Bristol NHS Foundation Trust, and Population Health Sciences, Bristol Medical School, University of Bristol, UK, for performing the searches. Publisher Copyright: © 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
Keywords: coeliac disease, diagnostic tests, meta-analyses

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Local EPrints ID: 453142
URI: http://eprints.soton.ac.uk/id/eprint/453142
ISSN: 0269-2813
PURE UUID: f3dcd6bd-7be4-48e4-a5cb-9e97bd0d923a
ORCID for Hazel Everitt: ORCID iD orcid.org/0000-0001-7362-8403

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Date deposited: 08 Jan 2022 22:34
Last modified: 17 Mar 2024 07:00

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Contributors

Author: Athena Sheppard
Author: Martha M.C. Elwenspoek
Author: Lauren J. Scott
Author: Victoria Corfield
Author: Hazel Everitt ORCID iD
Author: Peter M. Gillett
Author: Alastair D. Hay
Author: Hayley E. Jones
Author: Susan Mallett
Author: Jessica Watson
Author: Penny F. Whiting

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