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Autoimmune response to M3 muscarinic acetylcholine receptor in Sjogren's syndrome

Research Project

Project/Area Number 23791100
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionUniversity of Tsukuba

Principal Investigator

TSUBOI Hiroto  筑波大学, 医学医療系, 講師 (80580505)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsシェーグレン症候群 / M3ムスカリン作働性アセチルコリン受容体 / 自己抗体 / 自己反応性T細胞 / インターフェロンγ / 自己免疫疾患
Research Abstract

To clarify the pathogenic roles of autoimmune response to M3 muscarinic acetylcholine receptor (M3R) in Sjogren’s syndrome (SS)
1) the disease specificity of anti-M3R antibodies in SS
2) the detection of M3R reactive T cells in SS.
1) Anti-M3R antibodies were examined by M3R peptides (N terminal, 1st, 2nd, 3rdextracellular loops) based ELISA in sera from rheumatoid arthritis (RA) (N=21), systemic lupus erythematosus (SLE) (N=21), primary biliary cirrhosis (PBC) (N=84), and acquired anhidrosis (AA) (N=12)
Antibodies for N terminal were positive in 42.9% of RA, 28.6% of SLE, 90.5% of PBC, 16.7% of AA. Antibodies for 1stloop were positive in 33.3%, 28.6%, 72.6%, 0%, for 2ndloop, 33.3%, 57.1%, 76.2%, 0%, for 3rdloop, 33.3%, 28.6%, 69.0%, 0%, respectively. 2) PBMC isolated from SS (N=3) and controls (N=3) were stimulated with M3R mix peptides (N terminal, 1st, 2nd, 3rd extracellular loops). M3R reactive IFNγproducing CD4+T cells were detected by IFNγMACS cytokine secretion assay in one SS, but not in controls. In conclusion, it was revealed that anti-M3R antibodies were not SS-specific, and M3R reactive T cells were detected in SS.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (14 results)

All 2013 2012 2011 Other

All Journal Article (8 results) (of which Peer Reviewed: 6 results) Presentation (4 results) (of which Invited: 1 results) Remarks (2 results)

  • [Journal Article] Validation of different sets of criteria for the diagnosis of Sjogren's syndrome in Japanese patients2013

    • Author(s)
      Tsuboi H, Hagiwara S, Asashima H, Umehara H, Kawakami A, Nakamura H, Sano H, Tsubota K, Ogawa Y, Takamura E, Saito I, Inoue H, Nakamura S, Moriyama M, Takeuchi T, Tanaka Y, Hirata S, Mimori T, Matsumoto I, Sumida T
    • Journal Title

      Mod Rheumatol

      Volume: 23 Pages: 219-225

    • NAID

      10031167692

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The crucial roles of IFN-g in the development of M3 muscarinic acetylcholine receptor induced Sjogren's syndrome-like sialadenitis2013

    • Author(s)
      Iizuka M, Tsuboi H, Matsuo N, Kondo Y, Asashima H, Matsui M, Matsumoto I, Sumida T
    • Journal Title

      Mod. Rheumatol

      Volume: 23 Pages: 614-616

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of IgG4 class switch-related molecules in IgG4-related disease2012

    • Author(s)
      Tsuboi H, Matsuo N, Iizuka M, Tsuzuki S, Kondo Y, Tanaka A, Moriyama M, Matsumoto I, Nakamura S, Sumida T
    • Journal Title

      Arthritis Research and Therapy

      Volume: 14

    • NAID

      120007137060

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Generation and functional analysis of monoclonal antibodies against the second extracellular loop of human M3 muscarinic acetylcholine receptor2012

    • Author(s)
      Tsuboi H, Nakamura Y, Iizuka M, Matsuo N, Matsumoto I, Sumida T
    • Journal Title

      Mod. Rheumatol

      Volume: 22 Pages: 264-271

    • NAID

      10030615200

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anti-M3 muscarinic acetylcholine receptor antibodies in patients with Sjogren's syndrome2012

    • Author(s)
      Sumida T, Tsuboi H, Iizuka M, AsashimaH, Matsumoto I
    • Journal Title

      Mod. Rheumatol

    • NAID

      40019381268

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pathogenic role of anti-M3 muscarinic acetylcholine receptor immune response in Sjogren's syndrome2012

    • Author(s)
      Sumida T, Iizuka M, Asashima H, Tsuboi H, Matsumoto I
    • Journal Title

      Presse Med

      Volume: 41

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] シェーグレン症候群における抗M3ムスカリン作働性アセチルコリン受容体抗体2012

    • Author(s)
      坪井 洋人
    • Journal Title

      医学のあゆみ

      Volume: 242 Pages: 573-578

    • Related Report
      2012 Annual Research Report
  • [Journal Article] シェーグレン症候群の病態と抗M3ムスカリン作働性アセチルコリン受容体抗体2011

    • Author(s)
      坪井 洋人、飯塚 麻菜、住田 孝之
    • Journal Title

      Medical Practice

      Volume: 28 Pages: 1247-1250

    • Related Report
      2011 Research-status Report
  • [Presentation] 抗M3ムスカリン作働性アセチルコリン受容体(M3R)抗体とシェーグレン症候群(SS)2012

    • Author(s)
      坪井 洋人
    • Organizer
      第40回日本臨床免疫学会総会
    • Place of Presentation
      スポンサードシンポジウム自己抗体(東京)
    • Year and Date
      2012-09-28
    • Related Report
      2012 Final Research Report
  • [Presentation] 日本人シェーグレン症候群患者の診断における3つの診断基準の比較2012

    • Author(s)
      坪井 洋人
    • Organizer
      第21回日本シェーグレン症候群学会
    • Place of Presentation
      シンポジウム2(京都)
    • Year and Date
      2012-09-08
    • Related Report
      2012 Final Research Report
  • [Presentation] 抗M3ムスカリン作働性アセチルコリン受容体抗体とシェーグレン症候群2012

    • Author(s)
      坪井 洋人
    • Organizer
      第40回 日本臨床免疫学会総会
    • Place of Presentation
      京王プラザホテル
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] シェーグレン症候群(SS)における抗M3ムスカリン作働性アセチルコリン受容体(M3R)抗体の機能解析2011

    • Author(s)
      坪井 洋人、中村 友美、松尾 直美、飯塚 麻菜、松本 功、住田 孝之
    • Organizer
      第39回日本臨床免疫学会総会(招待講演)
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://www.md.tsukuba.ac.jp/clinical-med/rheumatology/

    • Related Report
      2012 Final Research Report
  • [Remarks] シェーグレン症候群の病因・病態の解明と抗原特異的治療戦略の構築

    • URL

      http://www.md.tsukuba.ac.jp/clinical-med/rheumatology/

    • Related Report
      2012 Annual Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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