[Principles of immunotherapy in insulin-dependent diabetes mellitus]

There is now convincing evidence that insulin-dependent (Type 1) diabetes mellitus is an immunological disease. This is derived from observations of a genetically determined predisposition, an association of recent-onset diabetes with viral infections, an inflammatory cell infiltrate affecting the islets of Langerhans, autoantibodies against islet cells, insulin, insulin receptors, and other organ-specific or non-organ-specific antigens, as well as abnormalities of cell-mediated immunity and of non-antigen specific mediators. Finally, recurrent diabetes in cases of pancreas transplantation in monozygotic twins discordant for insulin-dependent diabetes underlines the influence of an autoimmune insulitis. The current concept of the aetiopathogenesis of most cases of insulin-dependent diabetes is that in genetically susceptible individuals any form of damage to beta cells by viral, toxic, dietary or other environmental factors may initiate beta cell destruction and/or aberrant antigen expression, followed by a self-perpetuating, mostly cell-mediated autoimmune destruction of the insulin-producing cells. Successful immunoprevention in autoimmune diabetes models, on the basis of these recent concepts, led to the assumption that immunotherapy by means of immunomodulative or immunosuppressive drugs might be a possible tool in the treatment of patients with recent onset insulin-dependent (Type 1) diabetes mellitus.