Association of linkage between autoantigens and, ubiquitin. proteasome system in autoantibody production

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591271
• Research Category: Grant-in-Aid for Scientific Research (C)
• 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: Juntendo University
• Principal Investigator: TAKASAKI Yoshinari 順天堂大学, 医学部, 教授 (80154772)
• Project Period (FY): 2009 – 2011
• Keywords: autoantigen / proteasome / ubiquitin / autoantibody

Research Abstract

We studied immune response to components of proteasome using sera from patients with various connective tissue diseases by immunoblotting. Then, we found that there is a linkage of autoimmune response among components of proteasome and their binding proteins. In addition, We found that circulating proteasome detected by sandwich type ELISA is significantly associated with autoimmune response to proteasome and its binding proteins. These results suggested that the circulating ubiquitin-proteasome complex binding with autoantigens in association with its biologic function is playing an important role to induce autoimmune response to its binding antigens.

Research Products

• [Journal Article] Up-regulation of the endoplasmic reticulum transmembrane protein UNC93B in the B cells of patients with active systemic lupus erythematosus (2011)
  • Author(s): Nakano S, Morimoto S, Suzuki S, Watanabe T, Amano H, Takasaki Y
  • Journal Title: Rheumatology Volume: 49 Pages: 876-881
  • Peer Reviewed
• [Journal Article] Elevated serum level of circulating syndecan-1(CD138) in active systemic lupus erythematosus (2011)
  • Author(s): Minowa K, Amano H, Nakano S, Ando S, Watanabe T, Nakiri Y, Amano E, Tokano Y, Morimoto S, Takasaki Y
  • Journal Title: Autoimmunity Volume: 44 Pages: 357-362
  • Peer Reviewed
• [Journal Article] Anti-T cell immunoglobulin and mucin domain-2 monoclonal antibody exacerbates collagen-induced arthritis by stimulating B cells (2011)
  • Author(s): Kawamoto T, Abe Y, Ito J, Makino F, Kojima Y, Usui Y, Ma J, Morimoto S, Yagita H, Okumura K, Akiba H, Takasaki Y
  • Journal Title: Arthritis Res Volume: Ther13 Pages: R47
  • Peer Reviewed
• [Journal Article] Anti-Ro/SSA Antibodies Are an Independent Factor Associated with an Insufficient Response to Tumor Necrosis Factor Inhibitors in Patients with Rheumatoid Arthritis (2011)
  • Author(s): Matsudaira R, Tamura N, Sekiya F, Ogasawara M, Yamanaka K, Takasaki Y
  • Journal Title: J Rheumatol Volume: 38 Pages: 2346-2354
  • Peer Reviewed
• [Journal Article] Inhibitory effects of ZSTK474, a novel phosphoinositide 3-kinase inhibitor, on osteoclasts and collagen-induced arthritis in mice (2010)
  • Author(s): Toyama S, Tamura N, Haruta K, Karakida T, Mori S, Watanabe T, Yamori T, Takasaki Y
  • Journal Title: Arthritis Res Ther Volume: 12 Pages: 1-11
  • Peer Reviewed
• [Journal Article] Autoantibody to NA14 is an independent marker primarily for Sjogren's syndrome (2009)
  • Author(s): Nozawa K, Ikeda K, Satoh M, Reeves WH, Stewart CM, Li YC, Yen TJ, Rios RM, Takamori K, Ogawa H, Sekigawa I, Takasaki Y, Chan EK
  • Journal Title: Front Biosci Volume: 14 Pages: 3733-3739
  • Peer Reviewed
• [Journal Article] Anti-proteasome activator 28 α is a novel anti-cytoplasmic antibody in patients with systemic lupus erythematosus and Sjogren's syndrome (2009)
  • Author(s): Matsushita M, Matsudaira R, Ikeda K, Nawata M, Tamura N, Takasaki Y
  • Journal Title: Mod Rheumatol Volume: 19 Pages: 622-628
  • Peer Reviewed
• [Presentation] REGENERATING GENE(REG) 1 ALPHA PROMOTES PROGRESSION IN PATIENTS WITH RHEUMATOID ARTHRITIS (2011)
  • Author(s): Nozawa K, Fujishiro M, Takasaki Y, Sekigawa
  • Organizer: ANNUAL EUROPEAN CONGRESS OF RHEUMATOLOGY 2011
  • Place of Presentation: London, British
  • Year and Date: 2011-07-27
• [Presentation] The Role for TIM-2 in Collagen-Induced Arthritis (2010)
  • Author(s): Kawamoto T, Akiba H, Abe Y, Morimoto S, Yamaji K, Tamura N, Takasaki Y
  • Organizer: 74th Annual Scientific Meeting of American College of Rheumatology
  • Place of Presentation: Atlanta, USA
  • Year and Date: 2010-11-10
• [Presentation] Anti-Ro/SS-A antibody is an independent factor of insufficient response to anti-TNF-alpha monoclonal antibodies in patients with rheumatoid arthritis (2010)
  • Author(s): Matsudaira R, Tamura N, Sekiya F, Watanabe T, Ogasawara M, Takasaki Y
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: Rome
  • Year and Date: 2010-06-17
• [Presentation] Autoantibodies in Connective Tissue Diseases-Its Mechanism of Production and Clinical Significance (2009)
  • Author(s): Takasaki Y
  • Organizer: Asia Pacific League of Associations for Rheumatology with the Philippine Rheumatology Association
  • Place of Presentation: Manila, Philippine
  • Year and Date: 2009-11-27
• [Presentation] Prevalence and Clinical Significance of the Anti-p53 Antibody in Systemic Lupus Erythematosus (2009)
  • Author(s): Yamanaka K, Nakano S, Kanai Y, Asano M, Ikeda K, Thoyama S, Ishiyama K, Takasaki Y
  • Organizer: 73th Annual Scientific Meeting of American College of Rheumatology
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2009-10-19