Biologic similarities based on age at onset in oligoarticular and polyarticular subtypes of juvenile idiopathic arthritis.
OBJECTIVE
To explore biologic correlates to age at onset in patients with juvenile idiopathic arthritis (JIA) using peripheral blood mononuclear cell (PBMC) gene expression analysis.


METHODS
PBMCs were isolated from 56 healthy controls and 104 patients with recent-onset JIA (39 with persistent oligoarticular JIA, 45 with rheumatoid factor-negative polyarticular JIA, and 20 with systemic JIA). RNA was amplified and labeled using NuGEN Ovation, and gene expression was assessed with Affymetrix HG-U133 Plus 2.0 GeneChips.


RESULTS
A total of 832 probe sets revealed gene expression differences (false discovery rate 5%) in PBMCs from children with oligoarticular JIA whose disease began before age 6 years (early-onset disease) compared with those whose disease began at or after age 6 years (late-onset disease). In patients with early-onset disease, there was greater expression of genes related to B cells and less expression of genes related to cells of the myeloid lineage. Support vector machine analyses identified samples from patients with early- or late-onset oligoarticular JIA (with 97% accuracy) or from patients with early- or late-onset polyarticular JIA (with 89% accuracy), but not from patients with systemic JIA or healthy controls. Principal components analysis showed that age at onset was the major classifier of samples from patients with oligoarticular JIA and patients with polyarticular JIA.


CONCLUSIONS
PBMC gene expression analysis reveals biologic differences between patients with early-and late-onset JIA, independent of classification based on the number of joints involved. These data suggest that age at onset may be an important parameter to consider in JIA classification. Furthermore, pathologic mechanisms may vary with age at onset, and understanding these processes may lead to improved treatment of JIA.
Barnes
Michael G
MG
William S. Rowe Division of Pediatric Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. michael.barnes@cchmc.org
Grom
Alexei A
AA
Thompson
Susan D
SD
Griffin
Thomas A
TA
Luyrink
Lorie K
LK
Colbert
Robert A
RA
Glass
David N
DN
D000293:Adolescent; D000367:Age Factors; D017668:Age of Onset; D001171:Arthritis, Juvenile / Q000235:genetics* / Q000378:metabolism; D002648:Child; D005260:Female; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D025341:Principal Component Analysis