التفاصيل البيبلوغرافية
| العنوان: |
Identification of Unique Antigenic Determinants in the Amino Terminus of IA-2 (ICA512) in Childhood and Adult Autoimmune Diabetes: New Biomarker Development. |
| المؤلفون: |
Acevedo-Calado, Maria, James, Eddie A., Morran, Michael P., Pietropaolo, Susan L., Qin Ouyang, Arribas-Layton, David, Songini, Marco, Liguori, Marco, Casu, Anna, Auchus, Richard J., Shuai Huang, Liping Yu, Michels, Aaron, Gianani, Roberto, Pietropaolo, Massimo, Ouyang, Qin, Huang, Shuai, Yu, Liping |
| المصدر: |
Diabetes Care; Apr2017, Vol. 40 Issue 4, p561-568, 8p, 1 Diagram, 2 Charts, 3 Graphs |
| مصطلحات موضوعية: |
DIAGNOSIS of diabetes, EPITOPES, AUTOIMMUNE diseases, NEUROENDOCRINE system, AUTOANTIGENS, ANTIGENS, AUTOANTIBODIES, ENZYMES, TYPE 1 diabetes, TYPE 2 diabetes, PHOSPHATASES, RESEARCH funding, T cells, MONONUCLEAR leukocytes |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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