Study of pathogenic mechanism of autoimmune diseases using the evidence from anti-IL-6 therapy

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390299
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Wakayama Medical University
• Principal Investigator: NISHIMOTO Norihiro 和歌山県立医科大学, 医学部, 教授 (80273663)
• Co-Investigator(Kenkyū-buntansha): ADACHI Yasuo 和歌山県立医科大学, 医学部, 博士研究員 (10253882) ; SUGINO Hidehiko 大阪大学, 大学院・生命機能研究科, 助教 (70270577) ; MATSUTANI Takaji 和歌山県立医科大学, 医学部, 講師 (70372290) ; MURAKAMI Miho 和歌山県立医科大学, 医学部, 助教 (30595591)
• Project Period (FY): 2009 – 2011
• Keywords: リウマチ学

Research Abstract

We analyzed comprehensively gene expression profiles in patients with autoimmune diseases including rheumatoid arthritis(RA) and systemic lupus erythematosus(SLE) by DNA microarray and their correlation with the efficacy of anti-IL-6 therapy. S100 family was identified to be involved not only in inflammatory response but in bone metabolism in RA. In SLE patients, abnormal ATP synthesis and DNA repair were identified which may be involved in the pathogenesis of SLE.

Research Products

• [Journal Article] Serum level of oxidative stress marker is dramatically low in patients with rheumatoid arthritis treated with tocilizumab (2011)
  • Author(s): Hirao M, Yamasaki N, Oze H, Ebina K, Nampei A, Kawato Y, Shi K, Yoshikawa H, Nishimoto N, Hashimoto J.
  • Journal Title: Rheumatol Int
  • Peer Reviewed
• [Journal Article] Abnormal networks of immune response-related molecules in bone marrow cells from patients with rheumatoid arthritis as revealed by DNA microarray analysis (2011)
  • Author(s): Lee HM, Sugino H, Aoki C, Shimaoka Y, Suzuki R, Ochi K, Ochi T, Nishimoto N.
  • Journal Title: Arthritis Res Ther Volume: 13(3) Pages: R89
  • Peer Reviewed
• [Journal Article] Underexpression of mitochondrial-DNA encoded ATP synthesis-related genes and DNA repair genes in systemic lupus erythematosus (2011)
  • Author(s): Lee HM, Sugino H, Aoki C, Nishimoto N.
  • Journal Title: Arthritis Res Ther Volume: 13(2) Pages: R63
  • Peer Reviewed
• [Journal Article] Humanized anti-interleukin-6-receptor antibody(tocilizumab) monotherapy is more effective in slowing radiographic progression in patients with rheumatoid arthritis at high baseline risk for structural damage evaluated with levels of biomarkers, radiography, and BMI : data from the SAMURAI study (2011)
  • Author(s): Hashimoto J, Garnero P, van der Heijde D, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Yoshikawa H, Nishimoto N.
  • Journal Title: Mod Rheumatol Volume: 21 Pages: 10-15
  • Peer Reviewed
• [Journal Article] Cytokine networks in systemic lupus erythematosus (2010)
  • Author(s): Lee HM, Sugino H, Nishimoto N
  • Journal Title: J Biomed Biotechnol 2010 Volume: 2010 Pages: 676284
  • Peer Reviewed
• [Journal Article] DNA microarray analysis of rheumatoid arthritis susceptibility genes identified by genome-wide association studies(GWAS) (2010)
  • Author(s): Sugino H, Lee HM, Nishimoto N.
  • Journal Title: Arthritis Res Ther Volume: 12 Pages: 401
  • Peer Reviewed
• [Journal Article] Specifically modified osteopontin in rheumatoid arthritis fibroblast-like synoviocytes supports interaction with B cells and enhances IL-6 production (2009)
  • Author(s): Take Y, Nakata K, Hashimoto J, Tsuboi H, Nishimoto N, Ochi T, Yoshikawa H.
  • Journal Title: Arthritis Rheum Volume: 60 Pages: 3591-3601
  • Peer Reviewed
• [Journal Article] Interactions among type I and II interferon, tumor necrosis factor, and beta-estradiol on the regulation of immune response-related gene expressions in systemic lupus erythematosus (2009)
  • Author(s): Lee HM, Mima T, Sugino H, Aoki C, Adachi Y, Yoshio-Hoshino N, Matsubara K, Nishimoto N.
  • Journal Title: Arthritis Res Ther Volume: 11(1) Pages: R1
  • Peer Reviewed
• [Journal Article] Interaleukin-11 and paired immunoglobulin-like type 2 receptor alpha expression correlates with tha number of joints with active arthritis in systemic juvenile idiopathic arthritis (2009)
  • Author(s): Mima T, Ishikawa S, Aoki C, Yoshio-Hoshino N, Adachi Y, Imagawa T, Mori M, Tomiita M, Iwata N, Murata T, Miyoshi M, Takei S, Aihara Y, Yokota S, Matsubara K, Nishimoto N.
  • Journal Title: Ann Rheum Dis Volume: 68 Pages: 286-7
  • Peer Reviewed
• [Journal Article] Abnormal expression of the genes involved in cytokine networks and mitochondrial function in systemic juvenile idiopathic arthritis identified by DNA microarray analysis (2009)
  • Author(s): Ishikawa S, Mima T, Aoki C, Yoshio-Hoshino N, Adachi Y, Imagawa T, Mori M, Tomiita M, Iwata N, Murata T, Miyoshi M, Takei S, Aihara Y, Yokota S, Matsubara K, Nishimoto N.
  • Journal Title: Ann Rheum Dis Volume: 68 Pages: 264-72
  • Peer Reviewed
• [Presentation] Correlations between S100 gene expression levels and the local and systemic inflammatory markers(matrix metalloproteinase-3, MMP3 ; erythrocyte sedimentation rate, ESR) in rheumatoid arthritis patients (2011)
  • Author(s): Lee H, Sugino H, Aoki C, Murakami M, Matsutani T, Ochi T, Nishimoto N.
  • Organizer: ACR2011
  • Place of Presentation: Chiago. USA
  • Year and Date: 20111104-09
• [Presentation] Comparisons of MHC class I molecule xpressions in bone marrow(BM) cells and peripheral blood cells(PBCS) of rheumatoid rthritis(RA). (2011)
  • Author(s): Lee H, Sugino H, Aoki C, Adachi Y, Shimaoka Y, Ochi T, Nishimoto N.
  • Organizer: EULAR2011
  • Place of Presentation: London, United Kingdom
  • Year and Date: 20110525-28
• [Presentation] Suppression of interacellular s100A4 utilizing small interfering RNA inhibits osteoclast genesis (2011)
  • Author(s): Sugino H, Lee H, Ochi T, Nishimoto N.
  • Organizer: EULAR2011
  • Place of Presentation: London, United Kingdom
  • Year and Date: 20110525-28
• [Presentation] Gene expression profiling of S100 protein families in the peripheral blood from patients with RA, SLE, polyJIA and sJIA-correlation between S100A4 expression and jpint destruction (2009)
  • Author(s): Nishimoto N, Sugino H, Aoki C, Lee H, Matsubara K, Mima T
  • Organizer: EULAR 2009
  • Place of Presentation: Copenhagen. Denmark
  • Year and Date: 20090600
• [Presentation] The peripheral blood genes that account for predictability of clinical response to tocilizumab(TCZ) treatment, corticosteroid dose reduction, and serum IL-6 normalization at week 48 on systemic onset juvenile arthriris(sJIA)
  • Author(s): Nishimoto N, Kawata Y, Lee H, Aoki C, Sugino H, Imagawa T, Mori M, Tomiita M, Murata T, Miyoshi M, Takei S, Aihara Y, Ochi T, Yokota S
  • Organizer: ACR/ARHP2009
  • Place of Presentation: USA
• [Book] ADDRESSING UNMET MEDICAL NEEDS IN RHEUMATOID ARTHRITIS (2012)
  • Author(s): Nishimoto N, Murakami M, Mastutani T
  • Total Pages: 16
  • Publisher: Future Science Group E-Books Program