OBJECTIVE: To identify differences in
peripheral blood gene expression between patients with different subclasses of
juvenile idiopathic arthritis (JIA) and healthy controls in a multicenter study of patients with recent-onset JIA
prior to treatment with
disease-modifying antirheumatic drugs (
DMARDs) or
biologic agents. METHODS:
Peripheral blood mononuclear cells (
PBMCs) from 59 healthy children and 136 patients with JIA (28 with enthesitis-related
arthritis [ERA], 42 with persistent
oligoarthritis, 45 with
rheumatoid factor [RF]-negative
polyarthritis, and 21 with systemic disease) were isolated from
whole blood. Poly(A)
RNA was labeled using a commercial
RNA amplification and labeling system (NuGEN Ovation), and
gene expression profiles were obtained using commercial expression
microarrays (Affymetrix HG-U133 Plus 2.0). RESULTS: A total of 9,501 differentially expressed probe sets were identified among the JIA subtypes and controls (by
analysis of variance;
false discovery rate 5%). Specifically, 193, 1,036, 873, and 7,595 probe sets were different in
PBMCs from the controls compared with those from the ERA, persistent
oligoarthritis, RF-negative
polyarthritis, and systemic JIA patients, respectively. In patients with persistent
oligoarthritis, RF-negative
polyarthritis, and systemic JIA subtypes, up-regulation of genes associated with interleukin-10 (IL-10) signaling was prominent. A
hemoglobin cluster was identified that was underexpressed in ERA patients but overexpressed in systemic JIA patients. The influence of
JAK/STAT, ERK/
MAPK, IL-2, and
B cell receptor signaling pathways was evident in patients with persistent
oligoarthritis. In systemic JIA, up-regulation of innate
immune pathways, including IL-6,
Toll-like receptor/IL-1 receptor, and
peroxisome proliferator-activated receptor signaling, were noted, along with down-regulation of
gene networks related to
natural killer cells and
T cells. Complement and
coagulation pathways were up-regulated in systemic JIA, with a subset of these genes being differentially expressed in other subtypes as well. CONCLUSION: Expression analysis identified differentially
expressed genes in
PBMCs obtained early in the disease from patients with different subtypes of JIA and in healthy controls, providing evidence of immunobiologic differences between these forms of
childhood arthritis.
