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Altered immune profile from pre-diabetes to manifestation of type 1 diabetes
Division of Paediatrics & Diabetes Research Centre, Department of Clinical & Experimental Medicine, Faculty of Health Sciences, Linköping University.
Jönköping University, School of Health Science, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health Science, HHJ. Biomedical Platform.
2013 (English)In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 100, no 1, 74-84 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:While the mechanisms leading to β-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 GAD65, 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-1β, -6, -7, -10, -13, -17, IFN-γ and TNF-α) 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-β) 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-α 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 GAD65, 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.

Place, publisher, year, edition, pages
2013. Vol. 100, no 1, 74-84 p.
Keyword [en]
Type 1 diabetes, Pre-diabetes, Th1, Th2, Cytokines, Chemokines
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:hj:diva-21174DOI: 10.1016/j.diabres.2013.01.014PubMedID: 23485080OAI: oai:DiVA.org:hj-21174DiVA: diva2:621559
Available from: 2013-05-15 Created: 2013-05-15 Last updated: 2013-05-15Bibliographically approved

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