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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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2013/589451 |
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| author | Jana Vcelakova Radek Blatny Zbynek Halbhuber Michal Kolar Ales Neuwirth Lenka Petruzelkova Tereza Ulmannova Stanislava Kolouskova Zdenek Sumnik Pavlina Pithova Maria Krivjanska Dominik Filipp Katerina Stechova |
| author_facet | Jana Vcelakova Radek Blatny Zbynek Halbhuber Michal Kolar Ales Neuwirth Lenka Petruzelkova Tereza Ulmannova Stanislava Kolouskova Zdenek Sumnik Pavlina Pithova Maria Krivjanska Dominik Filipp Katerina Stechova |
| author_sort | Jana Vcelakova |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-4bd8b45aaf3f4dc0987a47f1c4b5e069 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-4bd8b45aaf3f4dc0987a47f1c4b5e0692025-02-03T06:07:57ZengWileyJournal of Diabetes Research2314-67452314-67532013-01-01201310.1155/2013/589451589451The Effect of Diabetes-Associated Autoantigens on Cell Processes in Human PBMCs and Their Relevance to Autoimmune Diabetes DevelopmentJana Vcelakova0Radek Blatny1Zbynek Halbhuber2Michal Kolar3Ales Neuwirth4Lenka Petruzelkova5Tereza Ulmannova6Stanislava Kolouskova7Zdenek Sumnik8Pavlina Pithova9Maria Krivjanska10Dominik Filipp11Katerina Stechova12Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, V Uvalu 84, 15006 Prague, Czech RepublicCentral European Biosystems, Nad Safinou II 365, 25242 Vestec, Czech RepublicCentral European Biosystems, Nad Safinou II 365, 25242 Vestec, Czech RepublicLaboratory of Genomics and Bioinformatics, Institute of Molecular Genetics AS CR, Prague, Czech RepublicDepartment of Immunobiology, Institute of Molecular Genetics, Czech Academy of Science, Videnska 1083, 14220 Prague, Czech RepublicDepartment of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, V Uvalu 84, 15006 Prague, Czech RepublicDepartment of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, V Uvalu 84, 15006 Prague, Czech RepublicDepartment of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, V Uvalu 84, 15006 Prague, Czech RepublicDepartment of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, V Uvalu 84, 15006 Prague, Czech RepublicDepartment of Internal Medicine, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, V Uvalu 84, 15006 Prague, Czech RepublicCentral European Biosystems, Nad Safinou II 365, 25242 Vestec, Czech RepublicDepartment of Immunobiology, Institute of Molecular Genetics, Czech Academy of Science, Videnska 1083, 14220 Prague, Czech RepublicDepartment of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, V Uvalu 84, 15006 Prague, Czech RepublicType 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.http://dx.doi.org/10.1155/2013/589451 |
| spellingShingle | Jana Vcelakova Radek Blatny Zbynek Halbhuber Michal Kolar Ales Neuwirth Lenka Petruzelkova Tereza Ulmannova Stanislava Kolouskova Zdenek Sumnik Pavlina Pithova Maria Krivjanska Dominik Filipp Katerina Stechova The Effect of Diabetes-Associated Autoantigens on Cell Processes in Human PBMCs and Their Relevance to Autoimmune Diabetes Development Journal of Diabetes Research |
| 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 |
| url | http://dx.doi.org/10.1155/2013/589451 |
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