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Autoimmune Mechanism of Inflammatory Muscle Disease by Myositis-specific Autnantibodies

Research Project

Project/Area Number 17591055
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionKeio University

Principal Investigator

HIRAKATA Michito  Keio University, School of Medicine, Assistant Professor (30199046)

Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordspolymyositis / dermatomyositis / autoantibodies / autoantigen / aminoacyl tRNA synthetase / aignal recognition particle / autoimmunity / immunogenetics / HLA class II / 筋炎特異自己抗体 / 抗SRP抗体 / 筋病理組織像 / 壊死性筋炎 / 治療抵抗性筋炎 / 抗アミノアシルtRNA合成酵素抗体 / 間質性肺炎 / 抗hPMS1抗体 / 抗DNA-PKcs抗体 / 抗Mi-2抗体
Research Abstract

[Clinical and immunological features in Japanese patients with anti-PMS1 autoantibodies] In the in vitro transcriptioin/translation immunoprecipitation assay, eleven sera that immunoprecipitated the 120 kDa polypeptide corresponding to the PMS 1 antigen, were identified. Among these 11 patients, 6 had the PM-overlap syndrome, 2 had DM, 2 had ILD, and 1 had SSc. Eight of 11 (73%) had myositis, while 6 (55%) had ILD and arthritis. In standard immunoprecipitation studies, patients with anti-PMS1 were noted to have other autoantibodies including anti-aminoacyl tRNA synthetases (anti-Jo-1: 1 patient, anti-EJ: 1 patient, anti-PL-7: 1 patient), anti-U1 RNP (3 patients), anti-Sm (2 patients), and anti-DNA topoisomerase I (1 patient) antibodies. It should be noted that these sera did not recognize other proteins involved in DNA repairand remodeling, as reported in North American patients. These results indicate that anti-PMS1 autoantibodies are associated with myositis-overlap syndrome and may … More assist in identification of patients at increased risk of ILD and arthritis.
[Genotypic features of Japanese patients with myositis-specific autoantibodies] To explore the possibility that restrictions on antigen presentation are a key factor, we determined the immunogenetic phenotype of 44 Japanese patients who had the autoantibodies in conjunction with inflammatory myopathy. (1) Ten of 14 patients (71%) with anti-HisRS (8 individuals) or and-ThrRS (2 individuals) had the DRB1*0405-DQA1*0303-DQB1*0401 haplotype, compared to 22% of the controls (odds ratio (OR)= 9, P=0.001) and 13 of these 14 individuals (93%) had DR4. (2) Five of 8 patients (63%) with anti-AlaRS had DRB1*1501-DQA1*0102-DQB1*0602, compared to 9% of healthy controls (OR=17.5, P=0.002). (3) Seven of 8 patients (88%) with anti-AsnRS had DR 2 (DRB1*1501/1502), compared to 33% of healthy controls. (4) Nine of 20 patients (45%) with anti-SRP had DR 8 (DRB1*0802/08032), compared to 20% of healthy controls. Our present results indicate that anti-HisRS and anti-ThrRS antibodies have an immunogenetic association that is distinctly different from that of anti-AlaRS and anti-AsnRS autoantibodies.
[Heterogeneity of Autoimmune Responses to the Signal Recognition Particle (SRP)] To investigate the mechanisms responsible for anti-SRP induction, we studied 36 Japanese patients with anti-SRP identified among approximately 15,000 patients with connective tissue diseases using immunoprecipitation (IPP) assays using conditions that dissociate the SRP into individual polypeptide and RNA components. Ten different patterns of binding to the individual polypeptides and the 7SL-RNA could be distinguished. Sera from 9 patients (25%) directly immunoprecipitated the naked 7SL-RNA; all of them had myositis without cutaneous features of DM or malignant disease. Twenty-four patients had antibodies to the 54 kDa polypeptide (the primary target for anti-SRP antibodies in North American patients); they had lower frequencies of arthritis, compared to the 12 lacked antibodies to this polypeptide (4% vs. 36%; P<0.05). These results indicate that the SRP must trigger B cells in patients with inflammatory muscle disease when autoantibodies to this particle are produced. Less

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (24 results)

All 2008 2007 2006 2005

All Journal Article (21 results) (of which Peer Reviewed: 5 results) Presentation (3 results)

  • [Journal Article] Longterm effect of intermittent cyclical etidronate therapy on corticosteroid-induced osteoporosis in Japanese with connective tissue disease:7-vear follow up2008

    • Author(s)
      Sato S, Hirakata M, et. al.
    • Journal Title

      J.Rheumatol. 35(1)

      Pages: 142-146

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and immunogenetic features of patients with autoantibodies to asparaginyl-transfer RNA synthetase2007

    • Author(s)
      Hirakata M, Suwa A, et. al.
    • Journal Title

      Arthritis Rheum 50(4)

      Pages: 1295-1303

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Clinical characteristics of Japanese patients with anti-OJ (anti-Isoleucyl-tRNA Synthetase) autoantibodies2007

    • Author(s)
      Sato S, Kuwana M and Hirakata M.
    • Journal Title

      Rheumatology 46(5)

      Pages: 842-845

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Clinical and immunogenetic features of patients with autoantibodies to asparaginyl-transfer RNA synthetase2007

    • Author(s)
      Hirakata, M., Suwa, A., Takada, T., Sato, S., Nagai, S., Genth, E., Song, Y. W., Mimori, T., and Targoff, I. N
    • Journal Title

      Arthritis Rheum 56(4)

      Pages: 1295-1303

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Clinical characteristics of Japanese patients with anti-OJ(anti-Isoleucyl-tRNA Synthetase)autoantibodies2007

    • Author(s)
      Sato, S., Kuwana, M., and Hirakata, M
    • Journal Title

      Rheumatology 46(5)

      Pages: 842-845

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Clinical and immunogenetic features of p atients with autoantibodies to asparaginyl-transfer RNA synthetase2007

    • Author(s)
      Hirakata M, Suwa A, et. al.
    • Journal Title

      Arthritis Rheum. 56(4)

      Pages: 1295-1303

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 多発性筋炎・皮膚筋炎における自己抗体とその臨床免疫学的意義2007

    • Author(s)
      平形 道人
    • Journal Title

      日本臨床免疫学会雑誌 30(6)

      Pages: 444-454

    • NAID

      10021242040

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Autoantibody to CD40 ligand in systemic lupuserythematosus : association with thrombocyto penia but not thromboembolism.2006

    • Author(s)
      Nakamura M, Hirakata M, et al.
    • Journal Title

      Rheumatology (Oxford) 45(2)

      Pages: 150-156

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Pneumocystisjirovecipnenmoniaassociatedwithlow-dose methotrexatetreatment for rheumatoid arthritis : report of two cases and review of the literatures.2006

    • Author(s)
      Kaneko Y, Hirakata M, et al.
    • Journal Title

      Modern Rheumatology 16(1)

      Pages: 36-38

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 自己抗体陽性者に対する対処法および自己抗体の臨床的意義.2006

    • Author(s)
      平形 道人
    • Journal Title

      内科 97(4)

      Pages: 583-590

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 抗Jo-1抗体およびその他の抗アミノアシルtRNA合成酵素抗体2006

    • Author(s)
      平形 道人
    • Journal Title

      リウマチ科 36(1)

      Pages: 32-38

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 膠原病診療のポイント : 多発性筋炎・皮膚筋炎2006

    • Author(s)
      平形 道人
    • Journal Title

      診断と治療 94(10)

      Pages: 1882-1888

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 抗Jo-1抗体2006

    • Author(s)
      平形 道人
    • Journal Title

      日本医師会雑誌 特別号 「生涯教育リシーズ70/最新 臨床検査のABC」 135特別号(2)

      Pages: 301-301

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Autoantibodies to a 140-kd polypeptide,CADM-140,in Japanese patients with clinically amyopathic dermatomyositis2005

    • Author(s)
      Sato S, Hirakata M, et. al.
    • Journal Title

      Arthritis Rheum 52(5)

      Pages: 1571-1576

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis2005

    • Author(s)
      Sato, S., Hirakata, M., Kuwana, M., Suwa, A., Inada, S., Mimori, T., Nishikawa, T., Oddis, C. V., Ikeda, Y
    • Journal Title

      Arthritis Rheum 52(5)

      Pages: 1571-1576

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Anti-aminoacyl tRNA synthetase autoantibodies.2005

    • Author(s)
      Hirakata M
    • Journal Title

      Internal Medicine 44(6)

      Pages: 527-528

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis.2005

    • Author(s)
      Sato S, Hirakata M, et al.
    • Journal Title

      Arthritis Rheum 52(5)

      Pages: 1571-1576

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Immune responses to DNA mismatch repair enzymes hMSH2 and hPMS1 in patients with pancreatic cancer, dermatomyositis and polymyositis.2005

    • Author(s)
      Okada T, Hirakata M, et al.
    • Journal Title

      Int J Cancer 116

      Pages: 925-933

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Clinical Characteristics of Japanese patients with anti-PL-7 (anti-Threonyl-tRNA Synthetase) autoantibodies.2005

    • Author(s)
      Sato S, Hirakata M, et al.
    • Journal Title

      Clin Exp Rheumatol 23(5)

      Pages: 609-615

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 多発性筋炎・皮膚筋炎.2005

    • Author(s)
      平形道人
    • Journal Title

      「日本医師会雑誌」特別号「わかりやすい免疫疾患」 134特別号(1)

      Pages: 183-187

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 診療の秘訣-多発性筋炎・皮膚筋炎の診療に際して2005

    • Author(s)
      平形道人
    • Journal Title

      Modern Physician 25(11)

      Pages: 1444-1445

    • Related Report
      2005 Annual Research Report
  • [Presentation] Clinical features of Japanese patients with anti-asparaginyl tRNA synthetase autoantibodies.The Immunogenetic backgrounds2007

    • Author(s)
      Hirakata M, Suwa A, et. al.
    • Organizer
      71st Annual Meeting of American College of Rheumatology
    • Place of Presentation
      Boston
    • Year and Date
      2007-11-10
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Clinical features of Japanese patients with anti-asparaginyl tRNA synthetase autoantibodies. The Immunogenetic backgrounds2007

    • Author(s)
      Hirakata, M., Suwa, A., Takada, T., Kaneko, Y., Sato, S., Kuwana, M
    • Organizer
      71th Annual Meeting of American College of Rheumatology
    • Place of Presentation
      Boston
    • Year and Date
      2007-11-10
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Clinical features of Japanese patients with anti-asparagimyl tRNA synthetase autoantibodies.The Immunogenetic backgrounds2007

    • Author(s)
      Hirakata M, Suwa A, et. al.
    • Organizer
      71st Annual Meeting of American College of Rheumatology
    • Place of Presentation
      Boston
    • Year and Date
      2007-11-10
    • Related Report
      2007 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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