Identification of Unique Antigenic Determinants in the Amino Terminus of IA-2 (ICA512) in Childhood and Adult Autoimmune Diabetes: New Biomarker Development
| العنوان: | Identification of Unique Antigenic Determinants in the Amino Terminus of IA-2 (ICA512) in Childhood and Adult Autoimmune Diabetes: New Biomarker Development |
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| المؤلفون: | Marco Liguori, Shuai Huang, Eddie A. James, David Arribas-Layton, Richard J. Auchus, Aaron W. Michels, Qin Ouyang, Roberto Gianani, Anna Casu, Liping Yu, Maria Acevedo-Calado, Massimo Pietropaolo, Marco Songini, Michael P. Morran, Susan L. Pietropaolo |
| المصدر: | Diabetes Care |
| بيانات النشر: | American Diabetes Association, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, medicine.medical_specialty, Adolescent, Emerging Technologies and Therapeutics, T-Lymphocytes, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, medicine.disease_cause, Autoantigens, Epitope, Autoimmunity, Epitopes, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Antigen, Internal medicine, Diabetes mellitus, Internal Medicine, Humans, Medicine, Receptor-Like Protein Tyrosine Phosphatases, Class 8, Child, Autoantibodies, Advanced and Specialized Nursing, Type 1 diabetes, Glutamate Decarboxylase, business.industry, Autoantibody, Middle Aged, medicine.disease, 3. Good health, Diabetes Mellitus, Type 1, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 2, Child, Preschool, Immunology, Leukocytes, Mononuclear, Biomarker (medicine), Female, business, Biomarkers |
| الوصف: | 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. |
| تدمد: | 1935-5548 0149-5992 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::561e692a5638a69390d99f2e4ab7dbafTest https://doi.org/10.2337/dc16-1527Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....561e692a5638a69390d99f2e4ab7dbaf |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19355548 01495992 |
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