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Abnormal expression of the genes involved in cytokine networks and mitochondrial function in systemic juvenile idiopathic arthritis identified by DNA maicroarray analysis.
  1. Satoru Ishikawa
  1. Laboratory of Immune Regulation, Graduate School of Frontier Bioscience, Osaka University, Japan
    1. Toru Mima
    1. Laboratory of Immune Regulation, Graduate School of Frontier Bioscience, Osaka University, Japan
      1. Chieko Aoki
      1. Laboratory of Immune Regulation, Graduate School of Frontier Bioscience, Osaka University, Japan
        1. Noako Yoshio-Hoshino
        1. Laboratory of Immune Regulation, Graduate School of Frontier Bioscience, Osaka University, Japan
          1. Yasuo Adachi
          1. Laboratory of Immune Regulation, Graduate School of Frontier Bioscience, Osaka University, Japan
            1. Tomoyuki Imagawa
            1. Department of Pediatrics, Yokohama City University School of Medicine, Japan
              1. Masaaki Mori
              1. Department of Pediatrics, Yokohama City University School of Medicine, Japan
                1. Minako Tomiita
                1. Department of Pediatrics, Graduate School of Medicine, Chiba University, Japan
                  1. Naomi Iwata
                  1. Aichi Children's Health and Medical Center, Japan
                    1. Takuji Murata
                    1. Department of Pediatrics, Osaka Medical College, Japan
                      1. Mari Miyoshi
                      1. Kobe Children's Hospital, Japan
                        1. Syuji Takei
                        1. Department of Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima Uni, Japan
                          1. Yukoh Aihara
                          1. Children's Medical Center, Yokohama City University Medical Center, Japan
                            1. Shumpei Yokota
                            1. Department of Pediatrics, Yokohama City University School of Medicine, Japan
                              1. Kenichi Matsubara
                              1. DNA Chip Research Inc., Japan
                                1. Norihiro Nishimoto (norihiro{at}fbs.osaka-u.ac.jp)
                                1. Graduate School of Frontier Biosciences, Osaka University, Japan

                                  Abstract

                                  Objectives: Systemic juvenile idiopathic arthritis (sJIA) is a rheumatic disease in childhood characterized by systemic symptoms and a relatively poor prognosis. Peripheral leukocytes are thought to play pathological roles in sJIA although the exact cause is still obscure. In this study, we aimed to clarify the cellular functional abnormality in sJIA.

                                  Methods: We analyzed the gene expression profile in peripheral leukocytes from 51 patients with sJIA, 6 patients with poly-articular type JIA (polyJIA) and 8 healthy children utilizing DNA microarrays. Gene ontology analysis and network analysis were performed on the genes differentially expressed in sJIA to clarify the cellular functional abnormalities.

                                  Result: A total of 3,491 genes were differentially expressed in patients with sJIA compared to healthy individuals. They were functionally categorized mainly into a defense-response group and a metabolism group according to gene ontology, suggesting the possible abnormalities in these functions. In the defense-response group, molecules predominantly constituting IFN-γ and TNF network cascades were up-regulated. In the metabolism group, oxidative phosphorylation-related genes were down-regulated, suggesting a mitochondrial disorder. Expression of mitochondrial DNA-encoded genes including cytochrome c oxidase (MT-CO) 1 and MT-CO2 were suppressed in patients with sJIA but not in patients with polyJIA or healthy children. However, nuclear DNA-encoded cytochrome c oxidases were intact.

                                  Conclusion: Our findings suggest that sJIA is not only an immunological disease but also a metabolic disease involving mitochondria disorder.

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