Specific gene expression profiles in systemic juvenile idiopathic arthritis

Abstract

Objective. Patients with systemic juvenile idiopathic arthritis (JIA) have arthritis, quotidian fevers, and other extraarticular features. This disease often remains severe and debilitating. The purpose of this study was to compare gene expression profiles in peripheral blood mononuclear cells (PBMCs) from patients with active and inactive systemic JIA to define and better understand the cause of active disease.Methods. Gene expression profiles of PBMCs were determined in cells from 9 patients with active systemic JIA and 8 patients with inactive systemic JIA. Unsupervised clustering and significance analysis were performed. We compared the systemic JIA profile with data from patients with polyarticular JIA, chronic infantile neurologic, cutaneous, articular syndrome, Kawasaki disease, and systemic lupus erythematosus to identify disease-specific genes. Quantitative reverse transcription-polymerase chain reaction of selected genes was performed on negatively selected B cells, T cells, and monocytes.Results. Unsupervised clustering of expressed genes resulted in 2 groups that corresponded to the clinical status of the patients (active and inactive disease) and was independent of their medications. A total of 286 genes were identified as significantly upregulated in patients with active disease and 86% of them were specific to systemic JIA. Interleukin-6 (IL-6) was expressed in monocytes and B cells, IL-10 in monocytes, and suppressor of cytokine signaling 3 in monocytes and T cells from patients with active disease.

Advances in the pathogenesis and treatment of systemic juvenile idiopathic arthritis

“…In this early study of nine patients with active s-JIA treated with recombinant IL-1 receptor antagonist, all of the subjects experienced a partial or complete response to treatment, further supporting the idea that IL-1 plays a key pathogenic role (19). This study contrasts slightly with others that did not find increased gene expression of IL-1β in the peripheral blood mononuclear cells of patients with s-JIA but did find upregulation of IL-1-initiated signaling pathways (14,20). Although the exact cellular source of IL-1 in s-JIA remains an open question, the clinical experience with IL-1-blocking agents, discussed below, confirms the important role of IL-1 in disease pathogenesis.…”

“…Gene expression profiles have shown increased expression of IL-6 in blood monocytes (and B-cells) in patients with active s-JIA compared with the expression in healthy controls (14). Additionally, serum IL-6 levels are significantly elevated in s-JIA patients compared with the same in healthy, age-matched controls.…”

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

“…Gene expression studies have also provided additional evidence that the role of the adaptive immune system is rather limited in systemic JIA as compared with the other JIA subtypes, whereas the contribution of the innate immunity may be much more prominent (19,25,26). Several recent gene expression (microarray) studies, for example, have shown that systemic JIA can be distinguished from other subtypes of JIA by the presence of an up-regulation of the innate immune pathways, including interleukin-6, Toll-like receptor/ interleukin-1 receptor, as well as a down-regulation of the gene networks involving T cell-related and MHCrelated biologic processes, including antigen presentation (19).…”

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.…”