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
07/01/2009Pubmed ID
19565504Pubmed Central ID
PMC2741130DOI
10.1002/art.24534Scopus ID
2-s2.0-67650045888 (requires institutional sign-in at Scopus site) 67 CitationsAbstract
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 DNMESH terms used to index this publication - Major topics in bold
AdolescentAntibodies, 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
