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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Hindawi Publishing Corporation
2013
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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. |
format | Online Article Text |
id | pubmed-3694381 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
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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