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


CONCLUSIONS
Gene expression signatures in PBMCs from patients with recent-onset polyarticular JIA reflect discrete disease processes and offer a molecular classification of disease.
Griffin
Thomas A
TA
William S. Rowe Division of Pediatric Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. grift0@cchmc.org
Barnes
Michael G
MG
Ilowite
Norman T
NT
Olson
Judyann C
JC
Sherry
David D
DD
Gottlieb
Beth S
BS
Aronow
Bruce J
BJ
Pavlidis
Paul
P
Hinze
Claas H
CH
Thornton
Sherry
S
Thompson
Susan D
SD
Grom
Alexei A
AA
Colbert
Robert A
RA
Glass
David N
DN
D000293:Adolescent; D000974:Antibodies, Antinuclear / Q000235:genetics; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001168:Arthritis / Q000145:classification* / Q000188:drug therapy / Q000235:genetics*; D001171:Arthritis, Juvenile / Q000145:classification* / Q000188:drug therapy / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D017781:Genes, Immediate-Early / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D005810:Multigene Family / Q000235:genetics; D012217:Rheumatoid Factor / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics
D000974:Antibodies, Antinuclear; D018501:Antirheumatic Agents; D016212:Transforming Growth Factor beta; D012217:Rheumatoid Factor; D008727:Methotrexate