Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets

Thomas A. Griffin, Michael G. Barnes, Norman T. Ilowite, Judyann C. Olson, David D. Sherry, Beth S. Gottlieb, Bruce J. Aronow, Paul Pavlidis, Claas H. Hinze, Sherry Thornton, Susan D. Thompson, Alexei A. Grom, Robert A. Colbert, David N. Glass

Research output: Contribution to journalArticle

50 Scopus 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 β-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.

Original languageEnglish (US)
Pages (from-to)2113-2123
Number of pages11
JournalArthritis and Rheumatism
Volume60
Issue number7
DOIs
StatePublished - Jul 1 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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    Griffin, T. A., Barnes, M. G., Ilowite, N. T., Olson, J. C., Sherry, D. D., Gottlieb, B. S., Aronow, B. J., Pavlidis, P., Hinze, C. H., Thornton, S., Thompson, S. D., Grom, A. A., Colbert, R. A., & Glass, D. N. (2009). Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets. Arthritis and Rheumatism, 60(7), 2113-2123. https://doi.org/10.1002/art.24534