Development of a novel disease severity marker for the inflammatory bowel diseases.

• Project/Area Number: 23659498
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Niigata University
• Principal Investigator: NAKATA Koh 新潟大学, 医歯学総合病院, 教授 (80207802)
• Co-Investigator(Kenkyū-buntansha): SUZUKI Kenji 新潟大学, 医歯学総合病院, 講師 (00303123)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 炎症学 / 内科 / 免疫学 / トランスレーショナルリサーチ / バイオテクノロジー / 蛋白症 / 潰瘍性大腸炎 / クローン病 / 肺胞蛋白症 / GM-CSF自己抗体 / ELISA法

Research Abstract

To develop a novel disease severity marker for Crohn's disease and ulceritive colitis, we invesitgated the concentration of IgG type and IgM type GM-CSF autoantibody concentrations in the sera from patients with Crohn's disease(n=44), ulcerative colitis(n=45), and normal subjects(n=43). The concentration of IgG antibody was under the detection limit in most subjects, but the concentration of IgM antibody was significantly higher in Crohn's disease than those in ulcerative disease and normal subjects. No significant correlation was found between the concentration and the disease severity.

Research Products

• [Journal Article] Bilateral peripheral infiltrates refractory to immunosuppressants were diagnosed as autoimmune pulmonary alveolar proteinosis and improved by inhalation of granulocyte/macrophage-colony stimulating factor. (2012)
  • Author(s): Satoh H, Tazawa R, SakakibaraT, Ohkouchi S, Ebina M, Miki M, Nakata K, Nukiwa T.
  • Journal Title: Intern Med. Volume: 51(13) Pages: 1737-42
  • Peer Reviewed
• [Journal Article] Runx1 deficiency in CD4+ T cells causes fatal autoimmune inflammatory lung disease due to spontaneous hyperactivation of cells. (2012)
  • Author(s): Wong WF, Kohu K, Nakamura A, Ebina M, Kikuchi T, Tazawa R, Tanaka K, Kon S, Funaki T. Sugahara-Tobinai A, Looi CY, Endo S, Funayama R, Kurokawa M, Habu S, Ishii N, Fukumoto M, Nakata K, Takai T, Satake M.
  • Journal Title: Intern Med. Volume: 188(11) Pages: 5408-5420
  • Peer Reviewed
• [Journal Article] IgM-type GM-CSF Autoantibody is Etiologically a Bystander but Associated with IgG-type Autoantibody Production in Autoimmune Pulmonary Alveolar Proteinosis. (2012)
  • Author(s): Nei T, Urano S, Motoi N, Takizawa J,Kaneko C,Kanazawa H,Tazawa R,Nakagaki K, Akagawa KS,Akasaka K, Ichiwata T Azuma A, Nakata K.
  • Journal Title: Am. J. Physiol. Volume: 302(9)
  • Peer Reviewed
• [Journal Article] Reduced GM-CSF autoantibody in improved lung of autoimune pulmonary alveolar proteinosis. (2012)
  • Author(s): Ohashi K, Sato A, Takada T, Inoue Y, Nakata K, Tazawa R.
  • Journal Title: Eur. Respir.J. Volume: 39(3) Pages: 777-780
  • Peer Reviewed
• [Journal Article] Direct evidence that GM-CSF inhalation improveslung clearance in pulmonary alveolar proteinosis. (2012)
  • Author(s): Ohashi K, Sato A, Takada T, Arai T, Nei T, Kasahara Y, Motoi N, Hojo M, Urano S, Ishii H, Yokoba M, Eda R, Nakayama H, Nasuhara Y, Tsuchihashi Y, Kaneko C, Kanazawa H, Ebina M, Yamaguchi E, Kirchner J, Inoue Y, Nakata K, Tazawa R.
  • Journal Title: Respir Med. Volume: 106(2) Pages: 284-293
  • Peer Reviewed
• [Journal Article] IgM-type GM-CSF autoantibody is etiologically a bystander but associated with IgG-type autoantibody production in autoimmune pulmonary alveolar proteinosis. (2012)
  • Author(s): Nei T, （10名略）Tazawa R, Nakata K.
  • Journal Title: Am J Physiol Lung Cell Mol Physiol. Volume: 302(9) Issue: 9 Pages: 1959-64
  • DOI: 10.1152/ajplung.00378.2011
  • Peer Reviewed
• [Journal Article] Runx1 deficiency in CD4+ T cells causes fatal autoimmune inflammatory lung disease due to spontaneous hyperactivation of cells. (2012)
  • Author(s): Wong WF, Tazawa R, （15名略）Nakata K, Takai T, Satake M.
  • Journal Title: J Immunol. Volume: 188(11) Issue: 11 Pages: 5408-5420
  • DOI: 10.4049/jimmunol.1102991
  • Peer Reviewed
• [Journal Article] Bilateral Peripheral Infiltrates Refractory to Immunosuppressants were Diagnosed as Autoimmune Pulmonary Alveolar Proteinosis and Improved by Inhalation of Granulocyte/Macrophage-Colony Stimulating Factor (2012)
  • Author(s): Satoh H, Tazawa R, （4名略）, Nakata K, Nukiwa T.
  • Journal Title: Internal Medicine Volume: 51 Issue: 13 Pages: 1737-1742
  • DOI: 10.2169/internalmedicine.51.6093
  • NAID: 130002062188
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Journal Article] Direct evidence that GM-CSF inhalation improves lung clearance in pulmonary alveolar proteinosis. (2012)
  • Author(s): Ohashi K, Sato A, Takada T,（18人略）Nakata K, Tazawa R.
  • Journal Title: Respir Med. Volume: 106(2) Pages: 284-293
  • Peer Reviewed
• [Journal Article] Identification of a mechanism for lung inflammation caused by Mycoplasma pneumoniae using a novel mouse model. (2011)
  • Author(s): Saraya T, Nakata K, Nakagaki K, Motoi N, Iihara K, Fujioka Y, Oka T, Kurai D, Wada H, Ishii H,Taguchi H, Kamiya S, Goto H.
  • Journal Title: Results in Immunology. Volume: 1(1) Pages: 76-87
  • Peer Reviewed
• [Journal Article] Vaccination with CD133+ melanoma induces specific Th17 and Th1 cell -mediated antitumor reactivity against parental tumor. (2011)
  • Author(s): Miyabayashi T, Kagamu H, Koshio J, Ichikawa K, Baba J, Watanabe S, Tanaka H, Tanaka J, Yoshizawa H, Nakata K, Narita I.
  • Journal Title: Cancer Immunol Immunother. Volume: 60(11) Pages: 1597-1608
  • Peer Reviewed
• [Journal Article] Indium-Tin Oxide Does Not Induce GM-CSF Autoantibodies. (2011)
  • Author(s): Masuko H, Hizawa N, Chonan T, Nakata K, Hebisawa A.
  • Journal Title: Am J Respir Crit Care Med. Volume: 184 Pages: 741-741
  • Peer Reviewed
• [Journal Article] Clinical features of secondary pulmonary alveolar proteinosis: pre-mortem cases in Japan. (2011)
  • Author(s): Ishii H, Tazawa R, Kaneko C, Saraya T, Inoue Y, Hamano E, Kogure Y, Tomii K, Terada M, Takada T, Hojo M, Nishida A, Ichiwata T, Trapnell BC, Goto H, Nakata K.
  • Journal Title: European Respir. J. Volume: 37(2) Pages: 465-468
  • Peer Reviewed
• [Journal Article] Identification of a mechanism for lung inflammation caused by Mycoplasma pneumoniae using a novel mouse model. (2011)
  • Author(s): Saraya T, Nakata K, Nakagaki K, Motoi N, Iihara K, Fujioka Y, Oka T, Kurai D, Wada H, Ishii H,Taguchi H, Kamiya S, Goto H.
  • Journal Title: Results in Immunology. Volume: 1 Pages: 76-87
  • Peer Reviewed
• [Journal Article] Efficacy and safety of sirolimus in lymphangioleiomyomatosis. (2011)
  • Author(s): Nakata K, （18人略）Trapnell BC.
  • Journal Title: N Engl J Med. Volume: 364 Pages: 1596-1606
  • Peer Reviewed
• [Journal Article] Vaccination with CD133+ melanoma induces specific Th17and Th1 cell－mediated antitumor reactivity against parental tumor. (2011)
  • Author(s): Miyabayashi T, Kagamu H, Koshio J, Ichikawa K, Baba J, Watanabe S, Tanaka H, Tanaka J, Yoshizawa H, Nakata K, Narita I.
  • Journal Title: Cancer Immunol Immunother. Volume: 60(11) Pages: 1597-1608
  • Peer Reviewed
• [Journal Article] 自己抗体の分子進化と肺胞蛋白症 (2011)
  • Author(s): 中田 光、根井 貴仁、中垣 和英
  • Journal Title: 綜合臨床 Volume: 60(12) Pages: 2494-2499
  • Peer Reviewed
• [Presentation] Pulmonary Alveolar Proteinosis (PAP) And Inhaled Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Therapy ?Clinical Features Predicting Recurrence (2012)
  • Author(s): R. Tazawa, T. Arai, T. Takada, Y. Kasahara, Y. Tsuchihashi, T. Nei, M. Hojo, H. Nakayama, M. Yokoba, H. Ishii, R. Eda,Y. Nasuhara, M. Ebina, M. Akira, E. Yamaguchi, Y. Inoue, K. Nakata.
  • Organizer: American Thoracic Society Annual Meeting.
  • Place of Presentation: San Francisco , U.S.A.
  • Year and Date: 2012-05-23
• [Presentation] IgM Type GM-CSF Autoantibody is Etiologically a Bystander but May be Involved in Development of IgG Type Autoantibody in Autoimmune Pulmonary Alveolar Proteinosis (2012)
  • Author(s): Nakata K, Nei T, Motoi N, Urano S, Tazawa R, Kanako C, Nakagaki K, Suzuki M,Takizawa J, Azuma A.
  • Organizer: American Thoracic Society Annual Meeting.
  • Place of Presentation: San Francisco , U.S.A.
  • Year and Date: 2012-05-23
• [Presentation] Evidence for Permeation of IgG type GM-CSF Autoantibody from the Circulation to the Lung in Autoimmune Pulmonary Alveolar Proteinosis (2012)
  • Author(s): Urano S, Akasaka K, Nei T, Motoi N, Tazawa R, Nakata K.
  • Organizer: American Thoracic Society Annual Meeting.
  • Place of Presentation: San Francisco , U.S.A.
  • Year and Date: 2012-05-23
• [Presentation] Repertoire Analysis of GM-CSF Autoantibody mRNA by Next Generation Sequencing In Autoimmune Pulmonary Alveolar Proteinosis (2012)
  • Author(s): Nakata K, Nei T, Motoi N, Urano S, Tazawa R, Nakagaki K, Suzuki M, Takizawa J, Azuma A.
  • Organizer: American Thoracic Society Annual Meeting
  • Place of Presentation: San Francisco , U.S.A.
  • Year and Date: 2012-05-23
• [Presentation] IgM Type GM-CSF Autoantibody is Etiologically a Bystander but May be Involved in Development of IgG Type Autoantibody in Autoimmune Pulmonary Alveolar Proteinosi. (2012)
  • Author(s): Nakata K, Nei T, Motoi N, Urano S, Tazawa R, Kanako C, Nakagaki K, Suzuki M, Takizawa J, Azuma A.
  • Organizer: American Thoracic Society Annual Meeting.
  • Place of Presentation: アメリカ
• [Presentation] Evidence for Permeation of IgG type GM-CSF Autoantibody from the Circulation to the Lung in Autoimmune Pulmonary Alveolar Proteinosis. (2012)
  • Author(s): Urano S, Akasaka K, Nei T, Motoi N, Tazawa R, Nakata K.
  • Organizer: American Thoracic Society Annual Meeting.
  • Place of Presentation: アメリカ
• [Presentation] Repertoire Analysis of GM-CSF Autoantibody mRNA by Next Generation Sequencing In Autoimmune Pulmonary Alveolar Proteinosis (2012)
  • Author(s): Nakata K, Nei T, Motoi N, Urano S, Tazawa R, Nakagaki K, Suzuki M, Takizawa J, Azuma A.
  • Organizer: American Thoracic Society Annual Meeting.
  • Place of Presentation: アメリカ
• [Presentation] Pulmonary Alveolar Proteinosis (PAP) And Inhaled Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Therapy―Clinical Features Predicting Recurrence. (2012)
  • Author(s): R. Tazawa, T. Arai, T. Takada, Y. Kasahara, Y. Tsuchihashi, T. Nei, M. Hojo, H. Nakayama, M. Yokoba, H. Ishii, R. Eda, Y. Nasuhara, M. Ebina, M. Akira, E. Yamaguchi, Y. Inoue, K. Nakata.
  • Organizer: Meet The Professor Meeting.
  • Place of Presentation: ドイツ
• [Presentation] Pulmonary alveolar Proteinosis : historic perspective (2011)
  • Author(s): Nakata K.
  • Organizer: PAP Update 2011
  • Place of Presentation: Pavia, Italy.
  • Year and Date: 2011-04-01
• [Presentation] Pulmonary alveolar Proteinosis: historic perspective (2011)
  • Author(s): Koh Nakata
  • Organizer: PAP Update 2011(招待講演)
  • Place of Presentation: Pavia, Italy
• [Book] 大学病院などの再生医療を支える細胞プロセッシング室運営マニュアル. (2012)
  • Author(s): 井上典子,梶昌美,小神晴美,渡辺真理,関根優,白山早起,藤本陽子,瀧澤淳,牧口智夫,布施一郎,中田光.
  • Total Pages: 142
  • Publisher: 株式会社ウイネット
• [Book] 今日の治療指針私はこう治療している (2012)
  • Author(s): 中田光
  • Publisher: 医学書院
• [Book] 大学病院などの再生医療を支える細胞プロセッシング室運営マニュアル (2012)
  • Author(s): 井上典子,梶正美,小神晴美, 渡辺真理,関根優,白山早起, 藤本陽子,瀧澤淳,牧口智夫, 布施一郎,中田光
  • Total Pages: 142
  • Publisher: 株式会社ウイネット
• [Book] 今日の治療指針 私はこう治療している 2012 (2012)
  • Author(s): 中田 光
  • Publisher: 医学書院
• [Book] EBM呼吸器疾患の治療 (2011)
  • Author(s): 高田俊範
  • Publisher: 中田光中外医薬社
• [Book] EBM 呼吸器疾患の治療 (2011)
  • Author(s): 高田 俊範、中田 光
  • Publisher: 中外医薬社