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

Anderson, Robert P, Henry, Margaret J, Taylor, Roberta, Duncan, Emma L, Danoy, Patrick, Cosat, Marylia J, Addison, Kathryn, Tye-Din, Jason A, Kotowicz, Mark A, Knight, Ross E, Pollock, Wendy, Nicholson, Geoffrey C, Toh, Ban-Hock, Brown, Matthew A and Pasco, Julie A 2013, A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways, BMC medicine, vol. 11, no. 1, Article 188, pp. 1-13.

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Title A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways
Author(s) Anderson, Robert P
Henry, Margaret J
Taylor, Roberta
Duncan, Emma L
Danoy, Patrick
Cosat, Marylia J
Addison, Kathryn
Tye-Din, Jason A
Kotowicz, Mark A
Knight, Ross E
Pollock, Wendy
Nicholson, Geoffrey C
Toh, Ban-Hock
Brown, Matthew A
Pasco, Julie A
Journal name BMC medicine
Volume number 11
Issue number 1
Season Article 188
Start page 1
End page 13
Total pages 13
Publisher BioMed Central
Place of publication London, UK
Publication date 2013
ISSN 1741-7015
Keyword(s) Celiac disease
Prevalence
Immunogenetics
Deamidated gliadin peptide
Transglutaminase
Serology
Epidemiology
Diagnosis
Summary 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.
Language eng
Field of Research 110307 Gastroenterology and Hepatology
Socio Economic Objective 920108 Immune System and Allergy
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2013, BioMed Central
Persistent URL http://hdl.handle.net/10536/DRO/DU:30060291

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.