Autoantibody markers for the diagnosis and prediction of type 1 diabetes.

Type 1 diabetes results from the autoimmune destruction of the insulin producing pancreatic beta-cells. For years, the notion that T-lymphocytes played a crucial role in the disorder's formation was considered such sound dogma, that interest in B-lymphocytes and autoantibodies as pathogenic variables was largely relegated to second-class status. However, much of our knowledge regarding the pathogenesis and natural history of this disease has been afforded by analysis of subjects having type 1 diabetes associated autoantibodies. While autoantibodies to more than two dozen autoantigens have been associated with this disease, a majority of interest has been directed at four autoantibodies; islet cell cytoplasmic (ICA), insulin (IAA), glutamic acid decarboxylase (GADA), and IA2/ICA512 autoantigen (IA2A). These autoantibodies, combined with other metabolic and genetic markers, are extremely effective for predicting eventual development of type 1 diabetes in otherwise healthy individuals. These autoantibodies have also aided in our understanding of disease heterogeneity and suggest that the autoimmune processes underlying type 1 diabetes initiate in the earliest stages of life (e.g., initial autoantibody formation at 9-18 months of age). Additional improvements are needed to more accurately define the time to disease onset, response to therapeutic intervention, the pathogenic features of the autoimmune response, and perhaps even the quantity of residual beta cell function.