Early detection of celiac disease: an exploration of clinical features and molecular biomarkers
In patients with celiac disease, the intake of gluten (dietary proteins present in grains) triggers an immune response that results in loss of the normal architecture of the small intestine. The diagnostic process for celiac disease has improved as anti-tissue transglutaminase antibodies have become available as a diagnostic markers. Nonetheless, population-based studies suggest that a substantial part of patients are not diagnosed. The overarching aim of this thesis is to contribute to better diagnosis of celiac disease.
The first part aimed to better describe the clinical presentation of celiac disease by exploring an adult patient cohort with regards to the symptoms at diagnosis, comorbidities and co-occurrence of immune-mediated diseases.The goal of the second part was to find new early biomarkers for celiac disease, using samples of a longitudinal study that included infants at high risk of developing celiac disease (PreventCD). This is the first study to indicate that changes in the circulating microRNA profile occur before the anti-transglutaminase antibodies can be detected in blood.In the last part of the thesis, disease specificity of these markers was illustrated by the observation that the microRNA profiles in another immune-mediated disease (multiple sclerosis) differ from the profiles associated with celiac disease.
The work presented in this thesis contributes to more awareness about the heterogeneous signs and symptoms of CeD in adults, thereby contributing to quicker diagnosis of CeD. The proposed biomarkers provide promising candidates for earlier diagnosis of CeD, which could lead to preventive strategies.