Th17/Treg-Related Transcriptional Factor Expression and Cytokine Profile in Patients With Rheumatoid Arthritis
ObjectivesThe aim of our study was to determine whether there is a correlation between transcription factors expression and Th17/Treg ratio, cytokine profile in the RA phenotype as well as to identify transcription factors that could be a potential biomarker for RA.MethodsThe study was conducted on...
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doaj-f87aa50deb3b4709b4f659c5fe2de04d2020-12-11T07:14:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-12-011110.3389/fimmu.2020.572858572858Th17/Treg-Related Transcriptional Factor Expression and Cytokine Profile in Patients With Rheumatoid ArthritisAgnieszka Paradowska-Gorycka0Anna Wajda1Katarzyna Romanowska-Próchnicka2Katarzyna Romanowska-Próchnicka3Ewa Walczuk4Ewa Kuca-Warnawin5Tomasz Kmiolek6Barbara Stypinska7Ewa Rzeszotarska8Dominik Majewski9Pawel Piotr Jagodzinski10Andrzej Pawlik11Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandDepartment of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandDepartment of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandDepartment of Pathophysiology, Warsaw Medical University, Warsaw, PolandDepartment of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandDepartment of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandDepartment of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandDepartment of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandDepartment of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandDepartment of Rheumatology and Internal Medicine, Poznan University of Medical Science, Poznan, PolandDepartment of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznan, PolandDepartment of Physiology, Pomeranian Medical University, Szczecin, PolandObjectivesThe aim of our study was to determine whether there is a correlation between transcription factors expression and Th17/Treg ratio, cytokine profile in the RA phenotype as well as to identify transcription factors that could be a potential biomarker for RA.MethodsThe study was conducted on 45 patients with RA, 27 patients with OA and 46 healthy controls (HCs). Th17 and Treg frequency was determined by flow cytometry (15 patients with RA/OA and 15 subjects of HC). Gene expression was estimated by qPCR, and the serum cytokine levels were determined by ELISA.ResultsThe percentage of Treg (CD4+CD25highCD127-) cells in RA patients was lower than in OA patients or HCs. Proportions of Th17 (CD4+CCR6+CXCR3-) cells were higher in RA and OA in comparison to HCs. STAT5 showed a very high expression in the blood of RA patients compared to healthy subjects. The expression of STAT5 and HELIOS was not detected in Th17 cells. A positive correlation between SMAD3 and STAT3 in RA patients was observed. Negative correlations between HIF-1A and SMAD2 in RA Treg cells and DAS-28 score were observed. The range of serum of IL-17 and IL-21 were higher in RA patients than in OA patients. Concentrations of serum IL-2 and IFN-γ were higher in RA and OA patients than in healthy subjects. Based on the ROC analysis, the diagnostic potential of the combination of HIF1A, SMAD3 and STAT3, was determined at AUC 0.95 for distinguishing RA patients from HCs. For distinguishing RA patients from OA patients the diagnostic potential of the combination of SMAD2, SMAD3, SMAD4 and STAT3, was determined at AUC 0.95.ConclusionBased on our study, we conclude that SMAD3 and STAT3 could be potential diagnostic biomarkers for RA.https://www.frontiersin.org/articles/10.3389/fimmu.2020.572858/fullrheumatoid arthritisTh17Tregtranscriptional factorgene expressionbiomarkers |
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English |
format |
Article |
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DOAJ |
author |
Agnieszka Paradowska-Gorycka Anna Wajda Katarzyna Romanowska-Próchnicka Katarzyna Romanowska-Próchnicka Ewa Walczuk Ewa Kuca-Warnawin Tomasz Kmiolek Barbara Stypinska Ewa Rzeszotarska Dominik Majewski Pawel Piotr Jagodzinski Andrzej Pawlik |
spellingShingle |
Agnieszka Paradowska-Gorycka Anna Wajda Katarzyna Romanowska-Próchnicka Katarzyna Romanowska-Próchnicka Ewa Walczuk Ewa Kuca-Warnawin Tomasz Kmiolek Barbara Stypinska Ewa Rzeszotarska Dominik Majewski Pawel Piotr Jagodzinski Andrzej Pawlik Th17/Treg-Related Transcriptional Factor Expression and Cytokine Profile in Patients With Rheumatoid Arthritis Frontiers in Immunology rheumatoid arthritis Th17 Treg transcriptional factor gene expression biomarkers |
author_facet |
Agnieszka Paradowska-Gorycka Anna Wajda Katarzyna Romanowska-Próchnicka Katarzyna Romanowska-Próchnicka Ewa Walczuk Ewa Kuca-Warnawin Tomasz Kmiolek Barbara Stypinska Ewa Rzeszotarska Dominik Majewski Pawel Piotr Jagodzinski Andrzej Pawlik |
author_sort |
Agnieszka Paradowska-Gorycka |
title |
Th17/Treg-Related Transcriptional Factor Expression and Cytokine Profile in Patients With Rheumatoid Arthritis |
title_short |
Th17/Treg-Related Transcriptional Factor Expression and Cytokine Profile in Patients With Rheumatoid Arthritis |
title_full |
Th17/Treg-Related Transcriptional Factor Expression and Cytokine Profile in Patients With Rheumatoid Arthritis |
title_fullStr |
Th17/Treg-Related Transcriptional Factor Expression and Cytokine Profile in Patients With Rheumatoid Arthritis |
title_full_unstemmed |
Th17/Treg-Related Transcriptional Factor Expression and Cytokine Profile in Patients With Rheumatoid Arthritis |
title_sort |
th17/treg-related transcriptional factor expression and cytokine profile in patients with rheumatoid arthritis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-12-01 |
description |
ObjectivesThe aim of our study was to determine whether there is a correlation between transcription factors expression and Th17/Treg ratio, cytokine profile in the RA phenotype as well as to identify transcription factors that could be a potential biomarker for RA.MethodsThe study was conducted on 45 patients with RA, 27 patients with OA and 46 healthy controls (HCs). Th17 and Treg frequency was determined by flow cytometry (15 patients with RA/OA and 15 subjects of HC). Gene expression was estimated by qPCR, and the serum cytokine levels were determined by ELISA.ResultsThe percentage of Treg (CD4+CD25highCD127-) cells in RA patients was lower than in OA patients or HCs. Proportions of Th17 (CD4+CCR6+CXCR3-) cells were higher in RA and OA in comparison to HCs. STAT5 showed a very high expression in the blood of RA patients compared to healthy subjects. The expression of STAT5 and HELIOS was not detected in Th17 cells. A positive correlation between SMAD3 and STAT3 in RA patients was observed. Negative correlations between HIF-1A and SMAD2 in RA Treg cells and DAS-28 score were observed. The range of serum of IL-17 and IL-21 were higher in RA patients than in OA patients. Concentrations of serum IL-2 and IFN-γ were higher in RA and OA patients than in healthy subjects. Based on the ROC analysis, the diagnostic potential of the combination of HIF1A, SMAD3 and STAT3, was determined at AUC 0.95 for distinguishing RA patients from HCs. For distinguishing RA patients from OA patients the diagnostic potential of the combination of SMAD2, SMAD3, SMAD4 and STAT3, was determined at AUC 0.95.ConclusionBased on our study, we conclude that SMAD3 and STAT3 could be potential diagnostic biomarkers for RA. |
topic |
rheumatoid arthritis Th17 Treg transcriptional factor gene expression biomarkers |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2020.572858/full |
work_keys_str_mv |
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