Type I insulin-dependent diabetes mellitus: a model for autoimmune polygenic disorders.
Insulin-dependent diabetes mellitus (IDD) affects between one in 250 and one in 500 Americans. The inheritance of IDD is non-Mendelian and polygenic. Genetic susceptibility predominantly results from specific alleles in the HLA complex and insulin gene region. Autoimmune destruction of pancreatic beta cells leads to profound insulinopenia (Atkinson and Maclaren, 1990). Without insulin treatment, fatal diabetic ketoacidosis results. Even with insulin treatment, after 10 to 20 years of IDD, devastating micro- and macrovascular complications lead to significant morbidity and premature mortality (Rosenbloom, 1983). In order to prevent this catastrophic disease and its consequences, we must understand the pathogenesis and immunogenetics of insulitis (the histologic lesion characteristic of IDD), whose ultimate expression is beta cell necrosis (Cudworth, 1978; Cahill and McDevitt, 1981; Eisenbarth, 1986). Current advances include recognition of new IDD-autoantigens (e.g., glutamic acid decarboxylase), susceptibility genes (e.g., HLA-DQB1*0201 and 0302), and the development of trials to prevent IDD through tolerization to IDD-autoantigens (e.g., insulin) (Maclaren, 1993; Winter et al., 1993). Unlocking the genetic mechanisms responsible for IDD can also reveal more general mechanisms involved in other organ-specific autoimmune diseases.
Winter
W E
WE
Department of Pathology and Laboratory Medicine, University of Florida, Gainesville 32610-0275, USA.
D000483:Alleles; D000917:Antibody Formation; D001323:Autoantibodies; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007111:Immunity, Cellular; D007515:Islets of Langerhans / Q000276:immunology; D008957:Models, Genetic
D001323:Autoantibodies; D006680:HLA Antigens