Specific gene expression profiles in systemic juvenile idiopathic arthritis

Arthritis Rheum. 2007 Jun;56(6):1954-65. doi: 10.1002/art.22644.

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 up-regulated 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.

Conclusion: Gene expression profiles in PBMCs identified disease-specific genes in patients with systemic JIA. Cell type analyses should allow further insight into the mechanisms of the disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Arthritis, Juvenile / genetics
  • Arthritis, Juvenile / metabolism*
  • Arthritis, Juvenile / physiopathology
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Child
  • Child, Preschool
  • Gene Expression Profiling*
  • Gene Expression Regulation / physiology*
  • Humans
  • Infant
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Monocytes / metabolism
  • Monocytes / pathology
  • Multigene Family / physiology
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • Up-Regulation / physiology

Substances

  • Interleukin-6
  • SOCS3 protein, human
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Interleukin-10