Immunological disorders of type 1 diabetes mellitus

The specific genes causing type 1 diabetes susceptibility in any species are unknown. Serological HLA studies have shown susceptibility to type 1 diabetes is linked to HLA DR3 and DR4 allels, whereas DR2 and DR5 alleles contain protective elements. DR4 chromosomes can be divided into diabetes prone or resistant by restriction fragment length polymorphism analyses with cDNA probes for DQ beta-gene. No type 1 diabetes-specific environmental factors have been revealed to be convincingly implicated in human type 1 diabetes. Congenital rubella, by its lasting influence on T cells creates susceptibility to many organ-specific autoimmune diseases. Certain dietary proteins shown in BB rats as well as hyperglycemia during the prenatal period increase the later incidence of type 1 diabetes. Human type 1 diabetes results from a progressive probably autoimmune loss of the pancreatic beta cells. The immunologic hallmarks of type 1 diabetes is the lymphocytic infiltration of pancreatic islets, the hyperexpression of class I MHC on all islet cells and the abarrent class II MHC expression on beta cells within inflamed islets, the increased frequency of activated T cells in islet and circulation. It is generally accepted that cellular immunity plays the major role in the pathogenesis of type 1 diabetes. The heightened autoimmune reactivity being detectable during the preclinical period, lasting months to years, has been proved by antibodies directed against cytoplasmic islet cell antigens (ICA), beta cell surface antigens (ICSA), insulin (IAA), and with a lower frequency against non-islet cell antigens. The presence of IgG insulin autoantibodies and complement fixing ICA confers increased risk for future type 1 diabetes development in genetically predisposed individuals than the presence of either marker alone. For ICSA a more specific and quantitative assay is needed. 90% of children developing type 1 diabetes were detected positive for ICA and/or IAA. By the time of clinical onset if type 1 diabetes some 90% of the insulin secretory beta cell mass has already been destroyed. For this reason, new approaches are needed to address the causes of diabetes and not just the consequences. The development of insulin-dependent diabetes may be reversible, or even preventable by early detection coupled with the judicious use of immunotherapy.