Dataset Information

Symptoms and signs in individuals with serology positive for celiac disease but normal mucosa.

ABSTRACT:

Background

Antibody serology is an important tool in the investigation of celiac disease (CD), but does not always correlate with mucosal appearance in the small intestine. Patients with positive CD serology but normal mucosa (Marsh 0) are at increased risk of future CD. In this study we describe a model for identifying and characterizing individuals with normal mucosa but positive CD serology. Such individuals are sometimes referred to as having latent CD.

Methods

The records of ten Swedish pathology departments were used to identify individuals with biopsies indicating normal duodenal/jejunal mucosa. Using the national personal identification number, these data were linked with CD serology data (antigliadin, antiendomysial and tissue transglutaminase antibodies); and we thereby identified 3,736 individuals with normal mucosa but positive CD serology. Two independent reviewers then manually reviewed their biopsy reports to estimate comorbidity. We also randomly selected 112 individuals for validation through patient chart review.

Results

The majority of the 3,736 individuals were females (62%). Children (0-15 years) made up 21.4%. The median number of biopsy specimen was 3. Our review of biopsy reports found that other gastrointestinal comorbidity was rare (inflammatory bowel disease: 0.4%; helicobacter pylori infection: 0.2%). Some 22% individuals selected for patient chart review had a relative with CD. The most common symptoms among these individuals were diarrhea (46%) and abdominal pain (45%), while 26% had anemia. Although 27% of the individuals selected for validation had been informed about gluten-free diet, only 13% were adhering to a gluten-free diet at the end of follow-up.

Conclusion

Individuals with positive CD serology but normal mucosa often have CD-like symptoms and a family history of CD.

SUBMITTER: Ludvigsson JF

PROVIDER: S-EPMC2724402 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Publications

Symptoms and signs in individuals with serology positive for celiac disease but normal mucosa.

Ludvigsson Jonas F JF Brandt Lena L Montgomery Scott M SM

BMC gastroenterology 20090722

<h4>Background</h4>Antibody serology is an important tool in the investigation of celiac disease (CD), but does not always correlate with mucosal appearance in the small intestine. Patients with positive CD serology but normal mucosa (Marsh 0) are at increased risk of future CD. In this study we describe a model for identifying and characterizing individuals with normal mucosa but positive CD serology. Such individuals are sometimes referred to as having latent CD.<h4>Methods</h4>The records of ...[more]

PMID: 19624815

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Project description:BackgroundGenomic prediction aims to leverage genome-wide genetic data towards better disease diagnostics and risk scores. We have previously published a genomic risk score (GRS) for celiac disease (CD), a common and highly heritable autoimmune disease, which differentiates between CD cases and population-based controls at a clinically-relevant predictive level, improving upon other gene-based approaches. HLA risk haplotypes, particularly HLA-DQ2.5, are necessary but not sufficient for CD, with at least one HLA risk haplotype present in up to half of most Caucasian populations. Here, we assess a genomic prediction strategy that specifically targets this common genetic susceptibility subtype, utilizing a supervised learning procedure for CD that leverages known HLA-DQ2.5 risk.MethodsUsing L1/L2-regularized support-vector machines trained on large European case-control datasets, we constructed novel CD GRSs specific to individuals with HLA-DQ2.5 risk haplotypes (GRS-DQ2.5) and compared them with the predictive power of the existing CD GRS (GRS14) as well as two haplotype-based approaches, externally validating the results in a North American case-control study.ResultsConsistent with previous observations, both the existing GRS14 and the GRS-DQ2.5 had better predictive performance than the HLA haplotype approaches. GRS-DQ2.5 models, based on directly genotyped or imputed markers, achieved similar levels of predictive performance (AUC = 0.718-0.73), which were substantially higher than those obtained from the DQ2.5 zygosity alone (AUC = 0.558), the HLA risk haplotype method (AUC = 0.634), or the generic GRS14 (AUC = 0.679). In a screening model of at-risk individuals, the GRS-DQ2.5 lowered the number of unnecessary follow-up tests for CD across most sensitivity levels. Relative to a baseline implicating all DQ2.5-positive individuals for follow-up, the GRS-DQ2.5 resulted in a net saving of 2.2 unnecessary follow-up tests for each justified test while still capturing 90 % of DQ2.5-positive CD cases.ConclusionsGenomic risk scores for CD that target genetically at-risk sub-groups improve predictive performance beyond traditional approaches and may represent a useful strategy for prioritizing individuals at increased risk of disease, thus potentially reducing unnecessary follow-up diagnostic tests.

Project description:Background & aimsCeliac disease is detected using serology and endoscopy analyses. We used multiple statistical analyses of a geographically isolated population in the United States to determine whether a single serum screening can identify individuals with celiac disease.MethodsWe performed a retrospective study of 3555 pediatric patients (18 years old or younger) in the intermountain West region of the United States from January 1, 2008, through September 30, 2013. All patients had undergone serologic analyses for celiac disease, including measurement of antibodies to tissue transglutaminase (TTG) and/or deamidated gliadin peptide (DGP), and had duodenal biopsies collected within the following year. Modified Marsh criteria were used to identify patients with celiac disease. We developed models to identify patients with celiac disease using logistic regression and classification and regression tree (CART) analysis.ResultsSingle use of a test for serum level of IgA against TTG identified patients with celiac disease with 90% sensitivity, 90% specificity, a 61% positive predictive value (PPV), a 90% negative predictive value, and an area under the receiver operating characteristic curve value of 0.91; these values were higher than those obtained from assays for IgA against DGP or IgG against TTG plus DGP. Not including the test for DGP antibody caused only 0.18% of celiac disease cases to be missed. Level of TTG IgA 7-fold the upper limit of normal (ULN) identified patients with celiac disease with a 96% PPV and 100% specificity. Using CART analysis, we found a level of TTG IgA 3.2-fold the ULN and higher to most accurately identify patients with celiac disease (PPV, 89%). Multivariable CART analysis showed that a level of TTG IgA 2.5-fold the ULN and higher was sufficient to identify celiac disease in patients with type 1 diabetes (PPV, 88%). Serum level of IgA against TTG in patients with versus those without trisomy 21 did not affect diagnosis predictability in CART analysis.ConclusionsIn a population-based study, we found that serum level of IgA against TTG can identify patients with celiac disease with PPVs of about 90%. Predictive values increase greatly when levels are markedly above the ULN or when the assay is used in combination with other variables. Measurement of IgG against TTG or DGP does not increase the accuracy of detection of celiac disease based against TTG IgA levels. There is a low risk of false-positive results from serologic analysis in patients with type I diabetes or persistent increases in antibody against TTG on repeat testing.

Dataset Information

Symptoms and signs in individuals with serology positive for celiac disease but normal mucosa.

Background

Methods

Results

Conclusion

Publications

Symptoms and signs in individuals with serology positive for celiac disease but normal mucosa.

Similar Datasets

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