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Pathogenesis of Type 1 Diabetes - Testing the Hygiene Hypothesis

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Hygiene increases chances for autoimmunity

According to the hygiene hypothesis, there is an association between the increased incidence and prevalence of immune-mediated diseases and a decreased exposure to pathogens. An EU-funded study is comparing three contrasting European populations with respect to standards of hygiene and living in order to identify risk factors that contribute to the aetiology of type 1 diabetes (T1D).

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The increased incidence of allergy and asthma in developed countries was initially explained by the hygiene hypothesis. Nowadays, this hypothesis has also been implicated as a factor contributing to the increased incidence of autoimmune diseases, such as T1D. One of the steepest gradients in standard of living worldwide is present at the border between Finland and Russian Karelia. The incidence of T1D is six times lower in Russian Karelia than it is in Finland, and this is not due to specific human leukocyte antigen (HLA) genotypes in the background population. Such borders provide a unique opportunity to define the impact of contrasting standards of hygiene and living on the appearance of signs of beta-cell autoimmunity and allergy in young children. On this basis, the aim of the EU-funded 'Pathogenesis of type 1 diabetes - Testing the hygiene hypothesis' (Diabimmune) project is to assess the role of the hygiene hypothesis in the development of T1D, and to define the mechanisms behind the potential protective effect conferred by microbial agents. The study design comprises two cohorts: a birth cohort and a cohort of young children. The objective is to study 1 500 children at the ages of 3 and 5 years and to observe 320 newborn infants with increased genetic risk for autoimmune disease from birth up to the age of 3 years in Estonia, Finland and Russian Karelia. Among the project's objectives are the study of the ontology of the immune system and analyses of the impact of gut microbial colonisation on immune system development. Other variables that will be investigated include regulatory T cell function, acute microbial infections and the consumption of foods that affect these microbes. For this purpose, the children included in the study are being tested for organ-specific autoantibodies, allergies, infections, gut microflora and nutritional factors. By comparing these parameters between children who develop beta-cell autoimmunity and those who present with allergy, scientists are hopeful that possible common pathogenic factors and pathways can be identified. The project is expected to generate novel knowledge that can be exploited for developing preventive strategies against the increasing incidence of T1D in most EU countries. The long-term goal is to mimic the mechanisms identified in the protective effect presenting in the Russian Karelian environment in order to devise intervention strategies such as the administration of safe microbial products.

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