ANTIISLET AUTOANTIBODIES IN DIABETES - CLINICAL-APPLICATIONS

The changing epidemiology of diabetes mellitus, our improved understan ding of its causes, and the advent of reliable and easily performed as says are propelling tests of islet autoimmunity into the clinical labo ratory. Type 1 diabetes mellitus is caused by autoimmune-mediated dest ruction of the insulin-producing, pancreatic beta cells in the Islets of Langerhans. Other forms of diabetes arise from defects of insulin a ction combined with milder degrees of beta cell deficiency. It is impo rtant to distinguish immune from non-immune forms of diabetes, since t he conditions are treated differently. Even so, it is often impossible to make this distinction on clinical grounds alone at the time hyperg lycemia is first recognized. Anti-islet autoantibodies are often detec table during the long, presymptomatic phase of type 1 diabetes. In add ition, autoantibodies, especially those that recognize the 65 kDa isof orm of glutamic acid decarboxylase (GAD(68)), are still found in many patients with type 1 diabetes long after their diagnosis is made. Isle t cell autoantibodies (ICA) are circulating markers of islet autoimmun ity that bind to multiple islet components and are detected by indirec t immunofluorescent labeling of frozen pancreas sections. The assay's 25 year history has been plagued by inter-laboratory inconsistencies. The identification of insulin, GAD(65), and protein tyrosine phosphata ses (IA-2 and IA-2 beta) as target autoantigens in type 1 diabetes has led to improved autoantibody assays. Since they incorporate purified, recombinant ligands, modern islet autoantibody assays are more easily performed and yield more consistent results than the ICA assay. Combi ning multiple autoantigens in a single test format allows improved sen sitivity and specificity for identifying islet autoimmunity. As automa ted methods are introduced, application of islet autoantibody testing to large populations is anticipated.