Pathogenesis and environmental factors contributing to celiac disease and opportunities for non-dietary therapies
OA Version
Citation
Abstract
Celiac Disease (CD) is a common autoimmune disease with a worldwide prevalence of 1%, and the incidence and prevalence rates appear to be trending upward. Compared to other autoimmune diseases, the genetic risk factors and environmental trigger for the disease are known. The genes encoding for Human Leukocyte Antigen (HLA)-DQ2 and HLA-DQ8 are highly associated with CD and the gluten protein gliadin triggers the inflammatory immune response, causing mucosal damage and villi atrophy. Highly sensitive and specific serology testing for tissue transglutaminase (tTG), endomysium (EmA) and deaminated gliadin peptide (DPG) antibodies are used in the initial screening for CD, and a duodenal endoscopy with biopsy is performed for confirmation of disease. The classical manifestations of CD include gastrointestinal (GI) symptoms and many other patients may experience extra-intestinal symptoms, typically including failure to thrive and anemia. Clinical manifestations of the disease may also differ based on age group and/or progression of the disease. One of the major complications of CD is refractory CD (RCD), which occurs in patients who adhere to a strict diet but continue to have atrophy of the villi and can possibly progress to enteropathy-associated t-cell lymphoma (EATL). Non-reactive CD (NRCD) is another, less severe, complication of CD also due to unresponsiveness to a gluten-free diet (GFD). Currently, the only treatment for CD is a strict GFD that is costly to some patients, and a portion of patients do not find relief despite adhering to the diet. Along with the complications of CD, certain diseases are highly associated with CD, and vice versa, with Type-1 Diabetes Mellitus (T1DM) and autoimmune thyroid disease being the most commonly associated diseases. However, not every individual with the high-risk HLA alleles goes on to develop CD when exposed to gluten. This suggests there are other non-genetic factors at play in CD, and this includes a variety of environmental factors. Prospective studies, such as The Environmental Determinants of Diabetes in the Young (TEDDY) and Celiac Disease Genomic, Environmental, Microbiome and Metabolomic (CDGEMM), have identified some of the environmental factors associated with CD and associated autoimmune disorders. While these studies have helped bridge the gaps in our understanding of the specific mechanisms involved in the pathogenies of CD, there is still a lack of knowledge of the exact role of environmental factors and associated diseases in the progression of CD. Further exploration of the environmental triggers of CD is warranted not only to find other treatments but to also be able to prevent the development of CD.