title: 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.
authors.affiliation: Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, V Uvalu 84, 15006 Prague, Czech Republic. jana.vcelakova@fnmotol.cz
authors.forename: Jana
authors.initials: J
authors.lastname: Vcelakova
authors.forename: Radek
authors.initials: R
authors.lastname: Blatny
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Halbhuber
authors.forename: Michal
authors.initials: M
authors.lastname: Kolar
authors.forename: Ales
authors.initials: A
authors.lastname: Neuwirth
authors.forename: Lenka
authors.initials: L
authors.lastname: Petruzelkova
authors.forename: Tereza
authors.initials: T
authors.lastname: Ulmannova
authors.forename: Stanislava
authors.initials: S
authors.lastname: Kolouskova
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Sumnik
authors.forename: Pavlina
authors.initials: P
authors.lastname: Pithova
authors.forename: Maria
authors.initials: M
authors.lastname: Krivjanska
authors.forename: Dominik
authors.initials: D
authors.lastname: Filipp
authors.forename: Katerina
authors.initials: K
authors.lastname: Stechova
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D001324:Autoantigens