Altered immune profile from pre-diabetes to manifestation of type 1 diabetes

Background: While the mechanisms leading to beta-cell destruction and clinical onset of T1D are still unclear, the composition of the immune profile is probably important for the outcome of immune activity. The aim of this study was to investigate the composition and possible changes of the immunological profile, spontaneously and following stimulation with the autoantigens GAD(65), and HSP60, at high-risk and T1D onset and further to 8 months post diagnosis. Methods: Fifteen first-degree relatives of T1D patients with a high risk of developing the disease within five years, 25 children approximately four days and 8 months after diagnosis of T1D and 16 healthy children were included in the study. Cytokines (IL-1 beta, -6, -7, -10, -13, -17, IFN-gamma and TNF-alpha) and chemokines (CCL2, -3, -4, -5 and CXCL10) associated with Th1, Th2, Tr1 and inflammatory cells were detected in cell culture supernatants by Luminex-technique, and markers associated with regulatory T-cells (FOXP3, CTLA-4 and TGF-beta) by real-time RT-PCR. Results: High-risk individuals differed in immunity from that seen in healthy and T1D children. High-risk individuals had a low TNF-alpha response and fewer responders from mitogen exposure as well as low spontaneous secretions of IL-13 compared to healthy children. High-risk individuals that later developed T1D, had a lower FOXP3 and CTLA-4 mRNA expression, following stimulation with GAD(65), in combination with higher secretion of the pro-inflammatory chemokine CCL4. Conclusion: Changes in immunity seen in individuals with high risk of developing T1D points to alterations/actions in the immune system already early in the pre-diabetic phase. (C) 2013 Elsevier Ireland Ltd. All rights reserved.