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Journal of Diabetes Research
Volume 2013 (2013), Article ID 589451, 10 pages
http://dx.doi.org/10.1155/2013/589451
Research Article

The Effect of Diabetes-Associated Autoantigens on Cell Processes in Human PBMCs and Their Relevance to Autoimmune Diabetes Development

1Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, V Uvalu 84, 15006 Prague, Czech Republic
2Central European Biosystems, Nad Safinou II 365, 25242 Vestec, Czech Republic
3Laboratory of Genomics and Bioinformatics, Institute of Molecular Genetics AS CR, Prague, Czech Republic
4Department of Immunobiology, Institute of Molecular Genetics, Czech Academy of Science, Videnska 1083, 14220 Prague, Czech Republic
5Department of Internal Medicine, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, V Uvalu 84, 15006 Prague, Czech Republic

Received 5 March 2013; Accepted 20 May 2013

Academic Editor: Jian Xiao

Copyright © 2013 Jana Vcelakova et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Type 1 Diabetes (T1D) is considered to be a T-helper- (Th-) 1 autoimmune disease; however, T1D pathogenesis likely involves many factors, and sufficient tools for autoreactive T cell detection for the study of this disease are currently lacking. In this study, using gene expression microarrays, we analysed the effect of diabetes-associated autoantigens on peripheral blood mononuclear cells (PBMCs) with the purpose of identifying (pre)diabetes-associated cell processes. Twelve patients with recent onset T1D, 18 first-degree relatives of the TD1 patients (DRL; 9/18 autoantibody positive), and 13 healthy controls (DV) were tested. PBMCs from these individuals were stimulated with a cocktail of diabetes-associated autoantigens (proinsulin, IA-2, and GAD65-derived peptides). After 72 hours, gene expression was evaluated by high-density gene microarray. The greatest number of functional differences was observed between relatives and controls (69 pathways), from which 15% of the pathways belonged to “immune response-related” processes. In the T1D versus controls comparison, more pathways (24%) were classified as “immune response-related.” Important pathways that were identified using data from the T1D versus controls comparison were pathways involving antigen presentation by MHCII, the activation of Th17 and Th22 responses, and cytoskeleton rearrangement-related processes. Genes involved in Th17 and TGF-beta cascades may represent novel, promising (pre)diabetes biomarkers.