Characterization of the autoimmune response against the nerve tissue S100[beta] in patients with type 1 diabetes

• Published in: Clinical and experimental immunology 2015-05, Vol.180 (2), p.207
• Main Authors: Gomez-Tourino, I, Simon-Vazquez, R, Alonso-Lorenzo, J, Arif, S, Calvino-Sampedro, C, Gonzalez-Fernandez, Á, Pena-Gonzalez, E, Rodriguez, J, Vinuela-Roldan, J, Verdaguer, J, Cordero, O J, Peakman, M, Varela-Calvino, R
• Format: Article
• Language: English
• Subjects: Diabetes; Pancreas; Rodents
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.12572

Summary Type 1 diabetes results from destruction of insulin-producing beta cells in pancreatic islets and is characterized by islet cell autoimmunity. Autoreactivity against non-beta cell-specific antigens has also been reported, including targeting of the calcium-binding protein S100[beta]. In preclinical models, reactivity of this type is a key component of the early development of insulitis. To examine the nature of this response in type 1 diabetes, we identified naturally processed and presented peptide epitopes derived from S100[beta], determined their affinity for the human leucocyte antigen (HLA)-DRB1*04:01 molecule and studied T cell responses in patients, together with healthy donors. We found that S100[beta] reactivity, characterized by interferon (IFN)-[gamma] secretion, is a characteristic of type 1 diabetes of varying duration. Our results confirm S100[beta] as a target of the cellular autoimmune response in type 1 diabetes with the identification of new peptide epitopes targeted during the development of the disease, and support the preclinical findings that autoreactivity against non-beta cell-specific autoantigens may have a role in type 1 diabetes pathogenesis.