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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 a...

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Autores principales: Vcelakova, Jana, Blatny, Radek, Halbhuber, Zbynek, Kolar, Michal, Neuwirth, Ales, Petruzelkova, Lenka, Ulmannova, Tereza, Kolouskova, Stanislava, Sumnik, Zdenek, Pithova, Pavlina, Krivjanska, Maria, Filipp, Dominik, Stechova, Katerina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694381/
https://www.ncbi.nlm.nih.gov/pubmed/23841104
http://dx.doi.org/10.1155/2013/589451
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author Vcelakova, Jana
Blatny, Radek
Halbhuber, Zbynek
Kolar, Michal
Neuwirth, Ales
Petruzelkova, Lenka
Ulmannova, Tereza
Kolouskova, Stanislava
Sumnik, Zdenek
Pithova, Pavlina
Krivjanska, Maria
Filipp, Dominik
Stechova, Katerina
author_facet Vcelakova, Jana
Blatny, Radek
Halbhuber, Zbynek
Kolar, Michal
Neuwirth, Ales
Petruzelkova, Lenka
Ulmannova, Tereza
Kolouskova, Stanislava
Sumnik, Zdenek
Pithova, Pavlina
Krivjanska, Maria
Filipp, Dominik
Stechova, Katerina
author_sort Vcelakova, Jana
collection PubMed
description 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.
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spelling pubmed-36943812013-07-09 The Effect of Diabetes-Associated Autoantigens on Cell Processes in Human PBMCs and Their Relevance to Autoimmune Diabetes Development Vcelakova, Jana Blatny, Radek Halbhuber, Zbynek Kolar, Michal Neuwirth, Ales Petruzelkova, Lenka Ulmannova, Tereza Kolouskova, Stanislava Sumnik, Zdenek Pithova, Pavlina Krivjanska, Maria Filipp, Dominik Stechova, Katerina J Diabetes Res Research Article 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. Hindawi Publishing Corporation 2013 2013-06-12 /pmc/articles/PMC3694381/ /pubmed/23841104 http://dx.doi.org/10.1155/2013/589451 Text en Copyright © 2013 Jana Vcelakova et al. https://creativecommons.org/licenses/by/3.0/ 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.
spellingShingle Research Article
Vcelakova, Jana
Blatny, Radek
Halbhuber, Zbynek
Kolar, Michal
Neuwirth, Ales
Petruzelkova, Lenka
Ulmannova, Tereza
Kolouskova, Stanislava
Sumnik, Zdenek
Pithova, Pavlina
Krivjanska, Maria
Filipp, Dominik
Stechova, Katerina
The Effect of Diabetes-Associated Autoantigens on Cell Processes in Human PBMCs and Their Relevance to Autoimmune Diabetes Development
title The Effect of Diabetes-Associated Autoantigens on Cell Processes in Human PBMCs and Their Relevance to Autoimmune Diabetes Development
title_full The Effect of Diabetes-Associated Autoantigens on Cell Processes in Human PBMCs and Their Relevance to Autoimmune Diabetes Development
title_fullStr The Effect of Diabetes-Associated Autoantigens on Cell Processes in Human PBMCs and Their Relevance to Autoimmune Diabetes Development
title_full_unstemmed The Effect of Diabetes-Associated Autoantigens on Cell Processes in Human PBMCs and Their Relevance to Autoimmune Diabetes Development
title_short The Effect of Diabetes-Associated Autoantigens on Cell Processes in Human PBMCs and Their Relevance to Autoimmune Diabetes Development
title_sort effect of diabetes-associated autoantigens on cell processes in human pbmcs and their relevance to autoimmune diabetes development
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694381/
https://www.ncbi.nlm.nih.gov/pubmed/23841104
http://dx.doi.org/10.1155/2013/589451
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