A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways

Anderson, R. P., Henry, M. J., Taylor, R., Duncan, Emma L, Danoy, P., Costa, M. J., Addison, K., Tye-Din, J. A., Kotowicz, M. A., Knight, R. E., Pollock, W., Nicholson, G. C., Toh, B. H., Brown, Matthew A., & Pasco, J. A. (2013) A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways. BMC Medicine, 11(1).

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Abstract

Background: Changing perspectives on the natural history of celiac disease (CD), new serology and genetic tests, and amended histological criteria for diagnosis cast doubt on past prevalence estimates for CD. We set out to establish a more accurate prevalence estimate for CD using a novel serogenetic approach.Methods: The human leukocyte antigen (HLA)-DQ genotype was determined in 356 patients with 'biopsy-confirmed' CD, and in two age-stratified, randomly selected community cohorts of 1,390 women and 1,158 men. Sera were screened for CD-specific serology.Results: Only five 'biopsy-confirmed' patients with CD did not possess the susceptibility alleles HLA-DQ2.5, DQ8, or DQ2.2, and four of these were misdiagnoses. HLA-DQ2.5, DQ8, or DQ2.2 was present in 56% of all women and men in the community cohorts. Transglutaminase (TG)-2 IgA and composite TG2/deamidated gliadin peptide (DGP) IgA/IgG were abnormal in 4.6% and 5.6%, respectively, of the community women and 6.9% and 6.9%, respectively, of the community men, but in the screen-positive group, only 71% and 75%, respectively, of women and 65% and 63%, respectively, of men possessed HLA-DQ2.5, DQ8, or DQ2.2. Medical review was possible for 41% of seropositive women and 50% of seropositive men, and led to biopsy-confirmed CD in 10 women (0.7%) and 6 men (0.5%), but based on relative risk for HLA-DQ2.5, DQ8, or DQ2.2 in all TG2 IgA or TG2/DGP IgA/IgG screen-positive subjects, CD affected 1.3% or 1.9%, respectively, of females and 1.3% or 1.2%, respectively, of men. Serogenetic data from these community cohorts indicated that testing screen positives for HLA-DQ, or carrying out HLA-DQ and further serology, could have reduced unnecessary gastroscopies due to false-positive serology by at least 40% and by over 70%, respectively.Conclusions: Screening with TG2 IgA serology and requiring biopsy confirmation caused the community prevalence of CD to be substantially underestimated. Testing for HLA-DQ genes and confirmatory serology could reduce the numbers of unnecessary gastroscopies. © 2013 Anderson et al.; licensee BioMed Central Ltd.

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ID Code: 87639
Item Type: Journal Article
Refereed: Yes
Keywords: Celiac disease, Deamidated gliadin peptide, Diagnosis, Epidemiology, Immunogenetics, Prevalence, Serology, Transglutaminase, gliadin, HLA DQ antigen, HLA DQ8 antigen, immunoglobulin A, immunoglobulin G, protein glutamine gamma glutamyltransferase 2, guanine nucleotide binding protein, protein glutamine gamma glutamyltransferase, abnormal laboratory result, adult, aged, allele, article, blood analysis, cohort analysis, controlled study, deamination, diagnostic error, female, genetic screening, genetic susceptibility, genotype, human, intestine biopsy, major clinical study, male, risk assessment, seroprevalence, Australia, biopsy, genetics, immunology, intestine, mass screening, middle aged, pathology, predictive value, prevention and control, procedures, Diagnostic Errors, Genetic Testing, GTP-Binding Proteins, HLA-DQ Antigens, Humans, Intestines, Predictive Value of Tests, Serologic Tests, Transglutaminases
DOI: 10.1186/1741-7015-11-188
ISSN: 1741-7015
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: © 2013 Anderson et al.
Copyright Statement: © Anderson et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Deposited On: 22 Sep 2015 03:02
Last Modified: 21 Nov 2016 05:34

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