GAD-65 AUTOANTIBODIES AND THEIR ROLE AS BIOMARKERS OF TYPE 1 DIABETES AND LATENT AUTOIMMUNE DIABETES IN ADULTS (LADA)

One of the hallmarks of autoimmune diabetes is the presence of adaptive responses directed against neuroendocrine proteins, such as glutamic acid decarboxylase (GAD). While GAD is widely distributed in neuroendocrine tissues, its specific significance in diabetes has paralleled the advances in understanding humoral and cellular immunity in type 7 diabetes (T1D) and in a subset of type 2 diabetes (T2D), going from the seminal discoveries of islet autoantibodies to the development and standardization of bioassays as diagnostic tools, to studies on the structure of GAD and its antigenic determinants. Autoantibodies targeting glutamate decarboxylase 2 (GAD-65) can accurately predict 170 development in combination with other surrogate humoral biomarkers and they are considered the most sensitive and specific biomarker to identify a subset of clinically diagnosed T2D termed latent autoimmune diabetes in adults (LADA). We and others provided evidence indicating that GAD-65 autoantibody detection should be part of the diagnostic assessment for clinically diagnosed T2DM, mainly because it predicts the rate of progression to insulin requirement in patients affected by LADA. More recently, GAD has been used as a tolerogenic vaccine to preserve beta cell function in autoimmune diabetes. While the results of phase Ill trials did not substantiate the earlier promise of phase I and II data, there are still many unanswered questions and approaches that need to be investigated in the applications of CAD in the therapy of T1D and LADA.