Autoantibody profile and epitope mapping in latent autoimmune diabetes in adults

The presence of islet cell autoantibodies in adult diabetic subjects who do not require insulin treatment for at least six months after the initial clinical diagnosis identifies the so-called latent autoimmune diabetes in the adult (LADA). Glutamic acid decarboxylase autoantibodies (GAD65Ab) are the best immune marker to identify LADA patients, while other islet autoantibodies, such as IA-2 autoantibodies, have a very low diagnostic sensitivity. Islet cell antibodies, as detected by indirect immunofluorescence, may improve the diagnostic specificity of the immune analysis when detected in GAD65Ab-positive patients. Although the majority of LADA patients progresses towards insulin dependency within a few years after the diagnosis, this form of diabetes is heterogeneous. The presence of high titers of GAD65Ab and/or GAD65Ab directed towards COOH-terminal epitopes of the autoantigen (GAD65-CAb) identifies a subgroup of LADA patients with clinical characteristics similar to those of typical type 1 diabetes and at very high risk of progression toward insulin dependency. On the other hand, low titers of GAD65Ab, or the exclusive presence of GAD65Ab directed to middle epitopes of the autoantigen, characterizes LADA patients with clinical characteristics almost indistinguishable from those of GAD65Ab-negative type 2 diabetic patients. LADA subjects, especially in the presence of high titers of GAD65Ab and/or GAD65-CAb, have an increased risk for other organ-specific autoimmune diseases such as thyroid autoimmune diseases or autoimmune Addison's. LADA should be considered a major component of the autoimmune polyendocrine syndromes, and screening for other autoimmune diseases should be performed in all LADA patients.