Abstract
BackgroundStudies have indicated that underdiagnosis and diagnostic delay are common in celiac disease. Therefore, it is important to increase our knowledge of what symptoms and biomarkers could identify undiagnosed cases of celiac disease.MethodsWe screened for celiac disease antibodies in stored blood samples from 16,776 participants in eight population-based studies examined during 1976–2012. Undiagnosed celiac seropositivity was defined as celiac disease antibody positivity (IgG-deamidated gliadin peptide above 10.0 U/mL and/or IgA-tissue transglutaminase (TTG) or IgG-TTG above 7.0 U/mL) without a known diagnosis of celiac disease in the National Patient Register. In all studies general health symptoms were recorded by participant-completed questionnaire, including self-perceived health, tiredness, headache and gastrointestinal symptoms. Furthermore, blood samples were drawn for analyses of biomarkers e.g. hemoglobin, blood glucose, cholesterol, liver parameters and vitamins. The participants with undiagnosed celiac seropositivity were matched by sex, age and study with four controls among the celiac disease antibody negative participants.ResultsWe excluded, five participants with known celiac disease, resulting in a population of 16,771 participants. In this population 1% (169/16,771) had undiagnosed celiac seropositivity. There were no statistically significant differences in symptoms between cases and controls. Undiagnosed celiac seropositivity was associated with low blood cholesterol (< 5 mmol/L) and low hemoglobin (< 7.3 mmol/L for women and < 8.3 mmol/L for men).ConclusionIn this general population study, undiagnosed cases of celiac seropositivity did not have more symptoms than controls, confirming the diagnostic difficulties of celiac disease and the low prognostic value of symptoms for a diagnosis of celiac disease. Furthermore, decreased levels of cholesterol and/or hemoglobin in the blood were associated with undiagnosed celiac seropositivity.
Highlights
Studies have indicated that underdiagnosis and diagnostic delay are common in celiac disease
We aimed to investigate whether participants with undiagnosed Celiac disease (CD), as defined by CD antibody positivity without a known diagnosis of CD, had more symptoms or affected biomarkers compared with CD antibody negative participants
16,776 participants with available serum were screened for CD antibodies by the EliATM Celikey® tissue transglutaminase (TTG) anti-IgA and anti-IgG assay, and deamidated gliadin peptide (DGP) anti-IgG assays, and 169 participants were identified with undiagnosed celiac seropositivity (Table 1).The measurements were performed at Thermo Fisher Scientific, ImmunoDiagnostics, Allerød, Denmark
Summary
Studies have indicated that underdiagnosis and diagnostic delay are common in celiac disease. There‐ fore, it is important to increase our knowledge of what symptoms and biomarkers could identify undiagnosed cases of celiac disease. Screening for CD among individuals without classical symptoms of CD or in the general population remains a controversial issue, e.g. because many screen-detected cases have few or no symptoms, and little is known about the prognosis of undiagnosed CD. We found no differences in symptoms before screening among participants with and without screen-detected CD [15], in line with other studies [16, 17]. This illustrates the difficulty of identifying CD by symptoms. We aimed to investigate whether participants with undiagnosed CD, as defined by CD antibody positivity without a known diagnosis of CD, had more symptoms or affected biomarkers compared with CD antibody negative participants
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