Immunology of Type 1 Diabetes

Type 1 diabetes (T1D) is an autoimmune disease that leads to the destruction of the beta-cells in the pancreas. T1D is one of the most common autoimmune diseases, especially in Finland where its incidence is the highest in the world.

T1D develops as a consequence of a combined effect of complex genetic predisposition and largely unknown environmental factors. Both murine and human studies suggest that the activation of autoreactive CD4+ and CD8+ T cells and autoantibody-producing B cells, as well as defects in regulatory T cell function, play a dominant role in T1D pathogenesis. 

In humans, the clinical manifestation of T1D is typically preceded by a preclinical phase in which diabetes-associated autoantibodies (DAAs) can be detected in the circulation. Subjects with multiple DAAs have an extremely high-risk of developing T1D, with a 5-year risk of around 50% and 15-year risk of over 80%. These findings suggest that the autoimmune process leading to T1D is initiated years before the clinical onset of the disease and progresses at different rates in different individuals. However, the immune pathways that lead from genetic susceptibility to islet autoimmunity and further to clinical disease remain poorly understood.