The genes influencing the susceptibility to IDDM in humans

Autoimmune diseases present a catastrophic sce­ nario for the human body: the immune system, usu­ ally poised to attack and remove invading pathogens such as bacteria or viruses, is now mis­ takenly engaged in an aggressive assault on the body's own tissues. In the case of insulin-depen­ dent diabetes mellitus (100M), one of the most prevalent autoimmune diseases, the target of the immune attack is the insulin-producing B cell of the pancreas. Once destroyed, the pancreatic islet B cells seldom regenerate; insulin production falls be­ Iowa critical level and the classical symptoms of the disease - polydipsia, polyuria, hyperglycemia, glycosuria and ketonemia - become manifest. Administration of exogenous insulin is sufficient to reverse these symptoms, but treatment must con­ tinue for the lifetime of the individual. Despite the administration of exogenous insulin, however, com­ plications, perhaps due to the extreme fluctuations in blood sugar levels, eventually become evident. Retinopathy, peripheral neuropathy and amputa­ tion of extremities due to poor circulation are some of the most severe examples. The development of 100M is the final outcome of multiple factors that act upon a predisposing ge­ netic background. Most investigators assume that the initial event that precipitates the onset of 100M is the entrance of a foreign antigen into an individ­ ual's body. The exact nature of this antigen remains the most perplexing puzzle in diabetes research; however, it is likely that it is a protein which, like most antigens, must undergo a "processing" step in order to be recognized by the immune system (1). Macrophages and dendritic cells biochemical­ ly cleave the protein antigen into its constitutive peptides, which are then displayed, bound to HLA class I and class II molecules, on the surface of these antigen presenting cells (1). Only the helper