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Identification of muscle specific autoantibodies for myasthenic syndromes and myositis by proteomic analysis

Research Project

Project/Area Number 20590993
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionGifu University

Principal Investigator

INUZUKA Takashi  Gifu University, 医学系研究科, 教授 (50184734)

Co-Investigator(Kenkyū-buntansha) HOZUMI Isao  岐阜大学, 医学系研究科, 准教授 (20242430)
TANAKA Yuji  岐阜大学, 医学系研究科, 助教 (70377654)
KIMURA Akio  岐阜大学, 医学系研究科, 助教 (00362161)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsプロテオミクス / 抗筋抗体 / 炎症性筋炎 / バイオマーカー / myosin-binding protein / pyruvate kinase isozyme / LC-MS / MSシステム / 二次元ブロット / 解糖系酵素 / 質量分析
Research Abstract

We identified two novel antibodies against muscle-specific components in sera of idiopathic inflammatory myopathies (IIMs) patients by proteomic analysis. These target antigens were myosin-binding protein C (MyBP C) and pyruvate kinase isozyme M1/M2 (PK M1/M2). MyBP C belongs to the immunoglobulin superfamily. PK catalyzes the conversion of phosphoenolpyruvate with regeneration of ATPs. Both molecules have been reported as possible myositogenic antigen for experimental autoimmune polymyositis.
The number of patients with the anti- MyBP C antibody was significantly higher among the IIM patients (9 of 10) than among the healthy control (1 of 10) and myotonic dystrophy (MyD) patients (5 of 11). The number of patients with the anti-PK M1/M2 antibody was significantly higher among the IIM patients (5 of 10) than among the healthy control (0 of 10) and myotonic dystrophy (MyD) patients (2 of 11). The sensitivity of this combination assay for diagnosis IIM was 50% and specificity was 80%. The sensitivity of this combination assay for diagnosis polymyositis was 71% and specificity was 92%. Therefore we propose that this combination assay is a candidate for further exploration as a diagnostic marker of IIM, particularly polymyositis.
To clarify the pathogenic roles of anti- MyBP C and PK M1/M2 antibodies in IIM, we must perform more experiments such as using animal models in which these antibodies are passively administrated.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (43 results)

All 2011 2010 2009 2008 Other

All Journal Article (28 results) (of which Peer Reviewed: 26 results) Presentation (14 results) Remarks (1 results)

  • [Journal Article] Antibodies in patients with neuropsychiatric systemic lupus erythematosus.2010

    • Author(s)
      Kimura A, Kanoh Y, Saukurai T, Koumura A, Yamada M, Hayashi Y, Tanaka Y, Hozumi I, Takemura M, Seishima M, Inuzuka T
    • Journal Title

      Neurology 74

      Pages: 1372-1379

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] High prevalence of autoantibodies against phosphoglycerate mutase 1 in patients with autoimmune central nervous system diseases.2010

    • Author(s)
      Kimura A, Sakurai T, Koumura A, SuzukiY, Tanaka Y, Hozumi I, Tanaka R, Takemura M, Seishima M, Inuzuka T
    • Journal Title

      J Neuroimmunology 219

      Pages: 105-108

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] No relapse of neuromyelitis optica during drug-induced B-lymphopenia with hypogammaglobulinemia.2010

    • Author(s)
      Tanaka Y, Kimura K, Kawachi I, Inuzuka T
    • Journal Title

      Neurology. 75

      Pages: 1745-1747

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 膠原病に伴う神経・筋障害-診断と治療の進歩膠原病における新たな抗神経抗体の検索2010

    • Author(s)
      木村暁夫, 犬塚貴
    • Journal Title

      日本内科学会雑誌 99

      Pages: 115-120

    • Related Report
      2010 Final Research Report
  • [Journal Article] Antibodies in patients with neuropsychiatric systemic lupus erythematosus.2010

    • Author(s)
      Kimura A, Kanoh Y, Saukurai T, Koumura A, Yamada M, Hayashi Y, Tanaka Y, Hozumi I, Takemura M, Seishima M, Inuzuka T.
    • Journal Title

      Neurology

      Volume: 74 Pages: 1372-1379

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Motor-dominant chronic inflammatory demyelinating polyneuropathy.2010

    • Author(s)
      Kimura A, Sakurai T, Koumura A, Suzuki Y, Tanaka Y, Hozumi I, Yoshino H, Yuasa T, Inuzuka T.
    • Journal Title

      J Neurology

      Volume: 257 Pages: 621-629

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High prevalence of autoantibodies against phosphoglycerate mutase 1 in patients with autoimmune central nervous system diseases.2010

    • Author(s)
      Kimura A, Sakurai T, Koumura A, Suzuki Y, Tanaka Y, Hozumi I, Tanaka R, Takemura M, Seishima M, Inuzuka T.
    • Journal Title

      J Neuroimmunology

      Volume: 219 Pages: 105-108

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serial monitoring of basal metabolic rate for therapeutic evaluation in an Issacs' syndrome patient with chronic fluctuating symptoms.2010

    • Author(s)
      Hayashi Y, Kimura A, Watanabe M, Yamada M, Sakurai T, Tanaka Y, Hozumi I, Inuzuka T.
    • Journal Title

      Internal medicine

      Volume: 49 Pages: 475-477

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Markedly ring-enhanced optic nerves due to metastasis of signet-ring cell gastric carcinoma. Internal medicine.2010

    • Author(s)
      Hayashi Y, Sakurai T, Tanaka Y, Yamada M, Koumura A, Kimura A, Hozumi I, Inuzuka T
    • Journal Title

      Internal medicine

      Volume: 49 Pages: 517-517

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High levels of copper, zinc, iron and magnesium, but not calcium, in the cerebrcspinal fluid of patients with Fahr's disease.2010

    • Author(s)
      Hozumi I, Koumura A, Kimura A, Hasegawa T, Honda A, Hayashi Y, Hashimoto K, Yamada M, Sakurai T, Tanaka Y, Satoh M, Inuzuka T
    • Journal Title

      Case Report of Neurology

      Volume: 2 Pages: 16-51

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 膠原病に伴う神経・筋障害-診断と治療の進歩膠原病における新たな抗神経抗体の検索.2010

    • Author(s)
      木村暁夫, 犬塚貴
    • Journal Title

      日本内科学会雑誌

      Volume: 99 Pages: 115-120

    • Related Report
      2010 Annual Research Report
  • [Journal Article] 特発性中脳水道狭窄症による閉塞性水頭症に対するV-Pシャント術の1年後から急速に進行するparkinsonismを呈した1例2010

    • Author(s)
      櫻井岳郎, 木村暁夫り 山田恵, 林祐一, 田中優司, 保住功, 犬塚貴
    • Journal Title

      BRAIN and NERVE

      Volume: 62 Pages: 527-531

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High prevalence of autoantibodies against phosphoglycerate mutase l in patients with autoimmune central nervous system diseases2010

    • Author(s)
      Kimura A, Sakurai T, Yamada M, Hayashi Y, Tanaka Y, Hozumi I, Tanaka R, Takemura M, Seishima M, Inuzuka T
    • Journal Title

      Journal of Neuroimmunology 219

      Pages: 105-108

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antibodies in patients with neuropsychiatric systemic lupus erythematosus2010

    • Author(s)
      Kimura A, Kanoh Y, Sakurai T, Koumura A, Yamada M, Hayashi Y, Tanaka Y, Hozumi I, Takemura M, Seishima M, Inuzuka T
    • Journal Title

      Neurology 74

      Pages: 1372-1379

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Motor-dominant chronic inflammatory demyelinating polyneuropathy.2010

    • Author(s)
      Kimura A, Sakurai T, Koumura A, Yamada M, Hayashi Y, Tanaka Y, Hozumi I, Yoshino H, Yuasa T, Inuzuka T
    • Journal Title

      Journal of Neurology 257

      Pages: 621-629

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 胃腸炎後に発症した抗GQ1B抗体陽性の小脳失調を伴わない急性一側性外転神経麻痺の1例2009

    • Author(s)
      櫻井岳郎, 田中優司, 木村暁夫, 保住功, 犬塚貴
    • Journal Title

      神経内科 71

      Pages: 514-516

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proteomic analysis of autoantibodies in neuropsychiatric systemic lupus erythematosus patient with white matter hyperintensities on brain MRI.2008

    • Author(s)
      Kimura A, Sakurai T, Tanaka Y, Hozumi I, Takahashi K, Takemura M, Saito K, Seishima M, Inuzuka T
    • Journal Title

      Lupus 17

      Pages: 16-20

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Longitudinal analysis of cytokines and chemokines in the cerebrospinal fluid of a patient with neuro-Sweet disease presenting with recurrent encephalomeningitis.2008

    • Author(s)
      Kimura A, Sakurai T, Koumura A, Suzuki Y, Tanaka Y, Hozumi I, Nakajima H, Ichiyama T, Inuzuka T
    • Journal Title

      Internal Medicine 47

      Pages: 135-141

    • NAID

      130000079753

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Progressive multifocal leuko-encephalopathy and CD4+ T-lymphocytopenia in a patient with Sjogren syndrome.2008

    • Author(s)
      Hayashi Y, Kimura A, Kato S, Koumura A, Sakurai T, Tanaka Y, Hozumi I, Sunden Y, Orba Y, Sawa H, Takahashi H, Inuzuka I
    • Journal Title

      J Neurol Sci. 268

      Pages: 195-198

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Selective cards, equine hypertrophy with idiopathic inflammation.2008

    • Author(s)
      Hayashi Y, Sakurai T, Kimura A, Ikeda T, Matsuyama Z, Suzuki Y, Tanaka Y, Hozumi I, Hosoe H, Takahashi H, Inuzuka T
    • Journal Title

      Muscle Nerve 38

      Pages: 1065-1069

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Creutafeldt-Jakob病と類似の臨床経過を示したBasedow病と伴った橋本脳症の1例2008

    • Author(s)
      櫻井岳郎, 田中優司, 香村彰宏, 林祐一, 木村暁夫, 保住功, 米田誠, 犬塚貴
    • Journal Title

      BRAIN and NERVE 60

      Pages: 559-565

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 介護従事者にみられた水痘脊髄炎2008

    • Author(s)
      鈴木真理子、林祐一、木村暁夫、永澤守、香村彰宏、櫻井岳郎、田中優司、保住功、犬塚貴
    • Journal Title

      BRAIN and NERVE 60

      Pages: 79-83

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Proteomic analysis of autoantibodies in neuropsychiatric systemic lupus erythematosus patient with white matter hyperintensities on brain MRI.2008

    • Author(s)
      Kimura A, Sakurai T, Tanaka Y, Hozumi I, Takahashi K, Takemura M, Saito K, Seishima M, Inuzuka T.
    • Journal Title

      Lupus 17

      Pages: 16-20

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of antibodies as biological markers in serum from multiple sclerosispatients by immunoproteomic approach.

    • Author(s)
      Sakurai T, Kimura A, Yamada M, Koumura A, Hayashi Y, Tanaka Y, Hozumi I, Inuzuka T
    • Journal Title

      J Neuroimmunology in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Elevated anti-heat shock protein 60 antibody titer is related to white matter hyperintensities.

    • Author(s)
      Kimura A, Sakurai T, Yamada M, Koumura A, Hayashi Y, Tanaka Y, Hozumi I, Takemura M, Seishima M, Inuzuka T
    • Journal Title

      Journal of stroke cerebrovascular disease in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Elevated anti-heat shock protein 60 antibody titer is related to white matter hype rintensities.

    • Author(s)
      Kimura A, Sakurai T, Yamada M, Koumura A, Hayashi Y, Tanaka Y, Hozumi I, Takemura M, Seishima M.Inuzuka T
    • Journal Title

      Journal of stroke cerebrovascular disease

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of antibodies as biological markers in serum from multiple sclerosis patients by immunoproteomic approach.

    • Author(s)
      Sakurai T, Kimura A, Yamada M, Koumura A, Hayashi Y, Tanaka Y, Hozumi I, Inuzuka T
    • Journal Title

      J Neuroimmunology

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Patterns of levels of biological metals in CSF differ among neurodegenerative diseases.

    • Author(s)
      Hozumi I, Hasegawa T, Honda A, Ozawa K, Hayashi Y, Hashimoto K, Yamada M, Koumura A, Sakurai T, Kimura A, Tanaka Y, Satoh M, Inuzuka T
    • Journal Title

      J Neurological Sciences

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Anti-Endothelial Cell Antibodies in the Elderly with Extended White Matter Hyperintensity.2011

    • Author(s)
      木村暁夫, 櫻井岳郎, 山田恵, 林祐一, 田中優司, 保住功, 犬塚貴
    • Organizer
      American Academy of Neurology 63^<st> Annual Meeting
    • Place of Presentation
      Honolulu, USA
    • Year and Date
      2011-04-13
    • Related Report
      2010 Final Research Report
  • [Presentation] Stress 70 protein抗体の特異性に関する検討2010

    • Author(s)
      櫻井岳郎、木村暁夫、山田恵、香村彰宏、林祐一、田中優司、保住功、犬塚貴
    • Organizer
      第51回日本神経学会総会
    • Place of Presentation
      東京
    • Year and Date
      2010-05-22
    • Related Report
      2010 Final Research Report
  • [Presentation] 通常型多発性硬化症における抗Stress 70 protein抗体の特異性に関する検討2010

    • Author(s)
      櫻井岳郎、木村暁夫、山田恵、香村彰宏、林祐一、田中優司、保住功、犬塚貴
    • Organizer
      第51回日本神経学会総会
    • Place of Presentation
      東京
    • Year and Date
      2010-05-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] Motor-dominant CIDP患者の臨床的検討2010

    • Author(s)
      木村暁夫、櫻井岳郎、山田恵、香村彰宏、林祐一、田中優司、保住功、犬塚貴
    • Organizer
      第51回日本神経学会総会
    • Place of Presentation
      東京
    • Year and Date
      2010-05-21
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] プロテオミクス解析を用いた通常型多発性硬化症における疾患特異的抗神経抗体の検索2009

    • Author(s)
      櫻井岳郎、木村暁夫、山田恵、林祐一、田中優司、保住功、犬塚貴
    • Organizer
      第50回日本神経学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2009-05-22
    • Related Report
      2010 Final Research Report
  • [Presentation] 多発性硬化症患者におけるPhosphoglycerate mutase 1抗体の特異性に関する検討2009

    • Author(s)
      櫻井岳郎、木村暁夫、山田恵、林祐一、田中優司、保住功、犬塚貴
    • Organizer
      第50回日本神経学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2009-05-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] 抗Hsp60抗体と大脳白質病変に関する研究2009

    • Author(s)
      木村暁夫、櫻井岳郎、山田恵、林祐一、田中優司、保住功、犬塚貴
    • Organizer
      第50回日本神経学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2009-05-20
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Identification of Antibodies Against Brain Antigen in Sera of Patients with Neuropsychiatric Systemic lupus erythematosus.2009

    • Author(s)
      木村暁夫, 櫻井岳郎, 山田恵, 林祐一, 田中優司, 保住功, 犬塚貴
    • Organizer
      American Academy of Neurology 61^<st> Annual Meeting
    • Place of Presentation
      Seattle, USA
    • Year and Date
      2009-04-29
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] 多発性硬化症患者における抗Phosphoglycerate mutase 1抗体の特異性に関する検討2009

    • Author(s)
      木村暁夫、櫻井岳郎、山田恵、林祐一、田中優司、保住功、犬塚貴
    • Organizer
      第21回日本神経免疫学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2009-03-13
    • Related Report
      2010 Final Research Report
  • [Presentation] プロテオミクス解析を用いた通常型多発性硬化症における疾患特異的抗神経抗体の検索2009

    • Author(s)
      櫻井岳郎、木村暁夫、山田恵、林祐一、田中優司、保住功、犬塚貴
    • Organizer
      第21回日本神経免疫学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2009-03-13
    • Related Report
      2010 Final Research Report
  • [Presentation] 通常型多発性硬化症における抗2008

    • Author(s)
      櫻井岳郎、木村暁夫、山田恵、香村彰宏、林祐一、田中優司、保住功、犬塚貴
    • Organizer
      第49回日本神経学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2008-05-16
    • Related Report
      2010 Final Research Report
  • [Presentation] CNSループス患者におけるプロテオミクス解析を用いた自己抗体認識抗原の同定2008

    • Author(s)
      木村暁夫、櫻井岳郎、山田恵、林祐一、田中優司、保住功、犬塚貴
    • Organizer
      第49回日本神経学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2008-05-16
    • Related Report
      2010 Final Research Report
  • [Presentation] Cプロテオミクス解析を用いた通常型多発性硬化症における疾患特異的抗神経抗体の検索2008

    • Author(s)
      木村暁夫, 櫻井岳郎, 山田恵, 林祐一, 田中優司, 保住功, 犬塚貴
    • Organizer
      第49回日本神経学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2008-05-16
    • Related Report
      2008 Annual Research Report
  • [Presentation] プロテオミクス解析を用いた中枢神経ループス特異的抗神経抗体の検索2008

    • Author(s)
      木村暁夫、櫻井岳郎、山田恵、林祐一、田中優司、保住功、犬塚貴
    • Organizer
      第20回日本神経免疫学会学術集会
    • Place of Presentation
      新潟
    • Year and Date
      2008-04-18
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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