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


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.


Jana Vcelakova1, Radek Blatny2, Zbynek Halbhuber2, Michal Kolar3, Ales Neuwirth4, Lenka Petruzelkova1, Tereza Ulmannova1, Stanislava Kolouskova1, Zdenek Sumnik1, Pavlina Pithova5, Maria Krivjanska2, Dominik Filipp4, and Katerina Stechova1

  • 1. Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prage and University Hospital Motel, V Uvalu 84, 15006 Prague, Czech Republic
  • 2. Central European Biosystems, Nad Safinou II 365, 25242 Vestec, Czech Republic
  • 3. Laboratory of Genomics and Bioinformatics, Institute of Molecular Genetics AS CR, Prague, Czech Republic
  • 4. Department of Immunobiology, Institute of Molecular Genetics, Czech Academy of Science, Videnska 1083, 1422 Prague, Czech Republic
  • 5. Department of Internal Medicine, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, V Uvalu 84, 15006 Prague, Czech Republic


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