Identification of Unique Antigenic Determinants in the Amino Terminus of IA-2 (ICA512) in Childhood and Adult Autoimmune Diabetes: New Biomarker Development
Year: 2017
Type: article
Study design: Observational Study
Abstract: OBJECTIVE The characterization of diverse subtypes of diabetes is a dynamic field of clinical research and an active area of discussion. The objective of this study was to identify new antigenic determinants in the neuroendocrine autoantigen IA-2 (ICA512) and assess whether circulating autoantibodies directed to new IA-2 epitopes identify autoimmune diabetes in young and adult populations with diabetes. RESEARCH DESIGN AND METHODS Clinically diagnosed patients with type 2 diabetes (n = 258; diabetes duration: 0.01–31 years) were evaluated using a new biomarker detecting autoantibodies directed to the extracellular domain of the neuroendocrine autoantigen IA-2 (IA-2ec). The proportion of IA-2ec autoantibodies was also evaluated in newly diagnosed patients with type 1 diabetes (n = 150; diabetes duration: 0.04–0.49 years). In addition, IA-2 (intracellular domain), GAD65, and zinc transporter 8 autoantibodies were assayed. RESULTS IA-2ec autoantibodies were detected in patients with type 1 diabetes and, surprisingly, in 5% of patients with type 2 diabetes without serologic responses to other IA-2 antigenic epitopes or other islet autoantigens. We also assessed the ability of IA-2ec–derived peptides to elicit CD4+ T-cell responses by stimulating peripheral blood mononuclear cells from patients with type 1 diabetes (n = 18) and HLA-matched healthy subjects (n = 13) with peptides and staining with the peptide/DQ8-specific tetramers, observing disease-associated responses to previously unreported epitopes within IA-2ec. CONCLUSIONS We developed a new antibody biomarker identifying novel antigenic determinants within the N terminus of IA-2. IA-2ec autoantibodies can be detected in patients with type 1 diabetes and in a subgroup of adult autoimmune patients with type 2 diabetes phenotype negative for conventional islet autoantibody testing. These observations suggest that islet autoimmunity may be more common in clinically diagnosed type 2 diabetes than previously observed.
Source: Diabetes Care
DOI: 10.2337/dc16-1527
Institutions: Baylor College of Medicine, University of Washington, Benaroya Research Institute, University of Toledo, Azienda Ospedaliera G. Brotzu, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, University of Michigan, Michigan Medicine, University of Colorado Anschutz, University of Colorado Denver, Rocky Vista University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: G2230976211, ENHANCEMENT OF BIOMARKERS FOR TYPE 1 DIABETES, Epidemiology of Heterogenity in Type 2 Diabetes, Michigan Institute for Clinical and Health Research (MICHR) (UL1), Michigan Institute for Clinical and Health Research (MICHR), Michigan Center for Diabetes Translational Research, Michigan Diabetes Research Center (MDRC), Insulin specific T cell response shaped by diabetes protective MHC class II molecules
OpenAlex ID: W2587394174