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Genomic characterization of remission in juvenile idiopathic arthritis

INTRODUCTION: The attainment of remission has become an important end point for clinical trials in juvenile idiopathic arthritis (JIA), although we do not yet have a full understanding of what remission is at the cell and molecular level. METHODS: Two independent cohorts of patients with JIA and hea...

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Autores principales: Jiang, Kaiyu, Frank, Mark Barton, Chen, Yanmin, Osban, Jeanette, Jarvis, James N
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4062846/
https://www.ncbi.nlm.nih.gov/pubmed/24000795
http://dx.doi.org/10.1186/ar4280
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author Jiang, Kaiyu
Frank, Mark Barton
Chen, Yanmin
Osban, Jeanette
Jarvis, James N
author_facet Jiang, Kaiyu
Frank, Mark Barton
Chen, Yanmin
Osban, Jeanette
Jarvis, James N
author_sort Jiang, Kaiyu
collection PubMed
description INTRODUCTION: The attainment of remission has become an important end point for clinical trials in juvenile idiopathic arthritis (JIA), although we do not yet have a full understanding of what remission is at the cell and molecular level. METHODS: Two independent cohorts of patients with JIA and healthy child controls were studied. RNA was prepared separately from peripheral blood mononuclear cells (PBMC) and granulocytes to identify differentially expressed genes using whole genome microarrays. Expression profiling results for selected genes were confirmed by quantitative, real-time polymerase chain reaction (RT-PCR). RESULTS: We found that remission in JIA induced by either methotrexate (MTX) or MTX plus a TNF inhibitor (etanercept, Et) (MTX + Et) is characterized by numerous differences in gene expression in peripheral blood mononuclear cells and in granulocytes compared with healthy control children; that is, remission is not a restoration of immunologic normalcy. Network analysis of the differentially expressed genes demonstrated that the steroid hormone receptor superfamily member hepatocyte nuclear factor 4 alpha (HNF4α) is a hub in several of the gene networks that distinguished children with arthritis from controls. Confocal microscopy revealed that HNF4a is present in both T lymphocytes and granulocytes, suggesting a previously unsuspected role for this transcription factor in regulating leukocyte function and therapeutic response in JIA. CONCLUSIONS: These findings provide a framework from which to understand therapeutic response in JIA and, furthermore, may be used to develop strategies to increase the frequency with which remission is achieved in adult forms of rheumatoid arthritis.
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spelling pubmed-40628462014-06-19 Genomic characterization of remission in juvenile idiopathic arthritis Jiang, Kaiyu Frank, Mark Barton Chen, Yanmin Osban, Jeanette Jarvis, James N Arthritis Res Ther Research Article INTRODUCTION: The attainment of remission has become an important end point for clinical trials in juvenile idiopathic arthritis (JIA), although we do not yet have a full understanding of what remission is at the cell and molecular level. METHODS: Two independent cohorts of patients with JIA and healthy child controls were studied. RNA was prepared separately from peripheral blood mononuclear cells (PBMC) and granulocytes to identify differentially expressed genes using whole genome microarrays. Expression profiling results for selected genes were confirmed by quantitative, real-time polymerase chain reaction (RT-PCR). RESULTS: We found that remission in JIA induced by either methotrexate (MTX) or MTX plus a TNF inhibitor (etanercept, Et) (MTX + Et) is characterized by numerous differences in gene expression in peripheral blood mononuclear cells and in granulocytes compared with healthy control children; that is, remission is not a restoration of immunologic normalcy. Network analysis of the differentially expressed genes demonstrated that the steroid hormone receptor superfamily member hepatocyte nuclear factor 4 alpha (HNF4α) is a hub in several of the gene networks that distinguished children with arthritis from controls. Confocal microscopy revealed that HNF4a is present in both T lymphocytes and granulocytes, suggesting a previously unsuspected role for this transcription factor in regulating leukocyte function and therapeutic response in JIA. CONCLUSIONS: These findings provide a framework from which to understand therapeutic response in JIA and, furthermore, may be used to develop strategies to increase the frequency with which remission is achieved in adult forms of rheumatoid arthritis. BioMed Central 2013 2013-08-30 /pmc/articles/PMC4062846/ /pubmed/24000795 http://dx.doi.org/10.1186/ar4280 Text en Copyright © 2013 Jiang et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Jiang, Kaiyu
Frank, Mark Barton
Chen, Yanmin
Osban, Jeanette
Jarvis, James N
Genomic characterization of remission in juvenile idiopathic arthritis
title Genomic characterization of remission in juvenile idiopathic arthritis
title_full Genomic characterization of remission in juvenile idiopathic arthritis
title_fullStr Genomic characterization of remission in juvenile idiopathic arthritis
title_full_unstemmed Genomic characterization of remission in juvenile idiopathic arthritis
title_short Genomic characterization of remission in juvenile idiopathic arthritis
title_sort genomic characterization of remission in juvenile idiopathic arthritis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4062846/
https://www.ncbi.nlm.nih.gov/pubmed/24000795
http://dx.doi.org/10.1186/ar4280
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