Immunotherapy of Type-1 Diabetes: Immunoprevention and Immunoreversal

Abstract

Type-1A diabetes (T1D) is characterized by a progressive insidious loss of self-tolerance to pancreatic islet beta cells resulting in their destruction and the development of overt hyperglycemia. Immunotherapy aims either to reverse the autoimmune process thereby preventing the development of the disease (immunoprevention) or to intervene at clinical diagnosis of type-1 diabetes and preserve residual b cell function (immunoreversal). Murine models and clinical studies of patients with type-1 diabetes have provided insights into the immunopathogenesis of type-1 diabetes and have led to the development of immunomodulatory therapeutic strategies. Recent clinical trials of anti-CD3 monoclonal antibody (mAbs) and glutamic acid decarboxylase (GAD) peptide have proven successful in attenuating loss of insulin production. Current individual clinical trials are investigating the use of anti-CD3 mAb, GAD, Rituximab, and Abatacept to maintain insulin responses. These trials will lay the groundwork for future studies in which more complete metabolic correction and immunologic tolerance will be restored, possibly with the use of combinations of therapies.