IMMUNOLOGY IN DIABETES - AN UPDATE

Type 1 (insulin-dependent) diabetes mellitus is strongly associated wi th autoimmune phenomena connected to the loss of beta-cells in the pan creatic islets. Despite considerable progress in our understanding of genetic susceptibility factors and islet autoimmunity preceding the cl inical onset of Type 1 diabetes there are considerable gaps in our kno wledge. First, the etiology is unclear. It is speculated that multiple etiological factors may initiate a common pathogenic pathway which re sults in immune-mediated beta-cell destruction. In 1998 we will need t o learn more about the possible importance of gestational infections, as well as isolation of viral DNA or RNA from the blood of new-onset p atients or marker-positive individuals. The scan of the whole genome h as provided a smorgasbord of genetic regions which confer diabetes ris k either alone or in combination. HLA remains the major genetic risk f actor, and while HLA peptide binding information is considerable, we u nderstand less of autoantigen processing and presentation. Cloned auto antigens and their use in standardized autoantibody assays have improv ed our ability to identify individuals at risk for diabetes. The diagn ostic sensitivity and specificity of autoantibody markers for Type 1 d iabetes are high as are their predictive values. We need methods to co mbine autoantibodies with genetic risk factors. The identification of individuals in different stages of their pathogenesis, including patie nts with so-called slowly progressive Type 1 diabetes (SPIDDM, LADA et c.), allow approaches to novel therapeutic interventions, Insulin is c urrently the therapeutic agent of choice and although spontaneous insu lin-dependent diabetes in the NOD mouse and the BB rat can be prevente d by immune suppression or modulation, this has not yet been possible in humans. The 1998 research on the interaction between environmental factors and susceptibility genes to initiate beta-cell specific autore activity should allow the development of therapies for prevention, and perhaps a cure, of insulin-dependent (Type 1) diabetes. (C) 1998 John Wiley & Sons, Ltd.