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

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.

Credits:

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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