Aaron W Michels1, Matthias von Herrath. 1. Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado 80045, USA. Aaron.Michels@ucdenver.edu
Abstract
PURPOSE OF REVIEW: To update on the clinical trials using antigen-specific therapies in autoimmune diabetes. RECENT FINDINGS: Type 1 diabetes is now a predictable disease with the measurement of islet autoantibodies, and the incidence is increasing dramatically. Well tolerated and effective interventions are needed to stop the underlying autoimmune destruction of insulin-producing beta cells. Beta-cell antigens, insulin and glutamic acid decarboxylase, are being used to preserve endogenous insulin production in individuals with new-onset diabetes and to prevent diabetes. The results of antigen-specific immune intervention trials are reviewed and consideration is given to future directions for inducing tolerance in type 1 diabetes. SUMMARY: Antigen-specific immune therapies act by enhancing regulatory T cell function, in animal models often locally and selectively in islets or pancreatic lymph nodes while inhibiting effector T cells. This therapeutic pathway provides a safe treatment to preserve beta cell function in new-onset diabetic individuals with the GAD-Alum vaccine being the most extensively studied therapy. Insulin is being used in many forms to prevent diabetes and stop the underlying autoimmune process. For the future, combination immune therapies targeting different pathways in the immune system will be needed to effectively induce sustained tolerance in type 1 diabetes.
PURPOSE OF REVIEW: To update on the clinical trials using antigen-specific therapies in autoimmune diabetes. RECENT FINDINGS:Type 1 diabetes is now a predictable disease with the measurement of islet autoantibodies, and the incidence is increasing dramatically. Well tolerated and effective interventions are needed to stop the underlying autoimmune destruction of insulin-producing beta cells. Beta-cell antigens, insulin and glutamic acid decarboxylase, are being used to preserve endogenous insulin production in individuals with new-onset diabetes and to prevent diabetes. The results of antigen-specific immune intervention trials are reviewed and consideration is given to future directions for inducing tolerance in type 1 diabetes. SUMMARY: Antigen-specific immune therapies act by enhancing regulatory T cell function, in animal models often locally and selectively in islets or pancreatic lymph nodes while inhibiting effector T cells. This therapeutic pathway provides a safe treatment to preserve beta cell function in new-onset diabetic individuals with the GAD-Alum vaccine being the most extensively studied therapy. Insulin is being used in many forms to prevent diabetes and stop the underlying autoimmune process. For the future, combination immune therapies targeting different pathways in the immune system will be needed to effectively induce sustained tolerance in type 1 diabetes.
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