Subtype‐specific peripheral blood gene expression profiles in recent‐onset juvenile idiopathic arthritis

Abstract

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 diseasemodifying antirheumatic drugs (DMARDs) or biologic agents. 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 proliferatoractivated 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. Methods

Advances in the pathogenesis and treatment of systemic juvenile idiopathic arthritis

“…Genes that were found to be uniquely upregulated in s-JIA compared with other subtypes included innate immune pathways (interleukin-6 (IL-6), toll-like receptor/IL-1 receptor, and peroxisome proliferator-activated receptor-γ (PPARγ) signaling). Genes related to natural killer cells and T-cells were downregulated (12). This recent understanding of the pathogenesis of s-JIA and the predominant role of the innate immune system has led to new therapeutic options that focus on inhibiting the effects of key proinflammatory cytokines.…”

Heterogeneity in juvenile idiopathic arthritis: Impact of molecular profiling based on DNA polymorphism and gene expression patterns

“…While these studies are large by gene expression standards, the cohorts are quite modest when compared with genomic cohorts. Nevertheless, gene expression profiles in peripheral blood mononuclear cells obtained prior to therapy with disease-modifying antirheumatic drugs can identify gene expression differences between groups of samples from patients with several JIA subtypes and those from normal controls (17). Further, gene expression analyses can identify phenotypically distinguishable subsets within JIA subtypes, including polyarticular JIA (18), systemic JIA (19), and oligoarticular JIA (20).…”

Comparison of biomarkers for systemic juvenile idiopathic arthritis

“…The innate immune system is believed to play an important role. An expansion of cells of monocyte/macrophage lineage during SJIA flare (9)(10)(11), with increased expression of corresponding genes, has been reported (8,9,(12)(13)(14). Crosstalk between the innate and adaptive immune system regulates a healthy inflammatory response.…”