Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets. Arthritis Rheum 2009 Jul;60(7):2113-23

Date

07/01/2009

Pubmed ID

19565504

Pubmed Central ID

PMC2741130

DOI

10.1002/art.24534

Scopus ID

2-s2.0-67650045888   50 Citations

Abstract

OBJECTIVE: To determine whether peripheral blood mononuclear cells (PBMCs) from children with recent-onset polyarticular juvenile idiopathic arthritis (JIA) exhibit biologically or clinically informative gene expression signatures.

METHODS: Peripheral blood samples were obtained from 59 healthy children and 61 children with polyarticular JIA prior to treatment with second-line medications, such as methotrexate or biologic agents. RNA was extracted from isolated mononuclear cells, fluorescence labeled, and hybridized to commercial gene expression microarrays (Affymetrix HG-U133 Plus 2.0). Data were analyzed using analysis of variance at a 5% false discovery rate threshold after robust multichip analysis preprocessing and distance-weighted discrimination normalization.

RESULTS: Initial analysis revealed 873 probe sets for genes that were differentially expressed between polyarticular JIA patients and healthy controls. Hierarchical clustering of these probe sets distinguished 3 subgroups within the polyarticular JIA group. Prototypical patients within each subgroup were identified and used to define subgroup-specific gene expression signatures. One of these signatures was associated with monocyte markers, another with transforming growth factor beta-inducible genes, and a third with immediate early genes. Correlation of gene expression signatures with clinical and biologic features of JIA subgroups suggested relevance to aspects of disease activity and supported the division of polyarticular JIA into distinct subsets.

CONCLUSION: Gene expression signatures in PBMCs from patients with recent-onset polyarticular JIA reflect discrete disease processes and offer a molecular classification of disease.

Author List

Griffin TA, Barnes MG, Ilowite NT, Olson JC, Sherry DD, Gottlieb BS, Aronow BJ, Pavlidis P, Hinze CH, Thornton S, Thompson SD, Grom AA, Colbert RA, Glass DN

Author

Judyann C. Olson MD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Antibodies, Antinuclear
Antirheumatic Agents
Arthritis
Arthritis, Juvenile
Case-Control Studies
Child
Child, Preschool
Female
Gene Expression Profiling
Genes, Immediate-Early
Humans
Leukocytes, Mononuclear
Male
Methotrexate
Multigene Family
Rheumatoid Factor
Transforming Growth Factor beta
jenkins-FCD Prod-480 9a4deaf152b0b06dd18151814fff2e18f6c05280