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Development of a clinical method to assess disease severity and treatment effect in idiopathic pulmonary alveolar proteinosis

Research Project

Project/Area Number 13671565
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionYokohama City University

Principal Investigator

YAMADA Yoshitsugu  Yokohama City University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (30166748)

Co-Investigator(Kenkyū-buntansha) KURAHASHI Kiyoyasu  Yokohama City University, School of Medicine, Assistant Professor, 医学部, 講師 (50234539)
NAKATA Koh  International Medical Center of Japan, Dept of Respiratory Diseases, Research Institute, Chief, 呼吸器疾患研究部, 室長 (80207802)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
Keywordsautoantibody / GM-CSF / idiopathic pulmonary alveolar proteinosis / epitope mapping / autoantibody titer / neutralizing activity / binding avidity and specificity / biochemical parameter / 特発性肺胞蛋白症(iPAP) / 抗GM-CSF自己抗体 / 皮下注療法 / 吸入療法 / 特発性肺胞蛋白症 / 顆粒球マクロファージコロニー刺激因子 / 中和抗体 / 重症度 / モニタリング / 治療効果 / 抗原認識部位 / KL-6 / CEA / AaCO2 / 特発性肺胞蛋白症の病勢
Research Abstract

Autoantibodies against granulocyte-marcophage colony-stimulating factor (GM-CSF) are consistently and specifically detected in the serum and bronchoalveolar lavage fluid (BALF) in the patients with idiopathic pulmonary alveolar proteinosis (iPAP). The concentration of the autoantibody is 81.9 (median, range 4.7-686.3) μg/ml in the serum and 1.15 (0.09-5.4) μg/ml in the BALF.
Autoantibodies against GMCSF have very high neutralizing activity and binding avidity, binding specificity. They recognize GMCSF superstructure. In iPAP patients, the autoantibodies against GM-CSF is proved to have enough capability to abrogate GM-CSF bioactivity in the lung. These results are published in the American Journal of Hematology.
Significant correlations are observed between those parameters which indicate disease severity (i.e. PaO2, A-aDO2, and DLCO) and serum biochemical parameters (i.e. CEA, KL-6, SP-A). However, serum and BALF concentrationsof the autoantibody and neutralizing activity of the autoantibody purified from the serum have no correlation with disease severity.
In 2 of 4 patients, the values of GM-CSF neutralizing activity in the serum paralleled the disease severity. This parameter has the possibility to be highly disease specific and minimum-invasive parameters for estimating disease severity of iPAP.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Uchida K, Nakata K, B.C.Tranpnell, Terakawa T, Hamano E, Mikami A, Matsushita I, J.F.Seymour, Oh-eda M, Ishige I, Eishi Y, Kitamura t, Yamada Y, Hanaoka K, Keicho N: "High-Affinity Autoantibodies Specifically Eliminate Granulocyte-Macrophage Colony-Stimulating Factor Activity in the Lungs of Patients with Idiopathic Pulmonary Alveolar Proteinosis"Blood. 103. 1089-1098 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Du H-L, Ohtsuji M, shigeta M, Chao DC, Sasaki K, Usuda Y, Yamada Y: "Expiratory asynchrony in proportional assist ventilation"Am.J.Respir.Crit.Care.Med.. 165. 972-977 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Du H-L, Amato MB, Yamada Y: "Closed-loop control of mechanical ventilation.(Automation of expiratory trigger sensitivity in pressure support ventilation)"Respir Care Clinics of North America. 7(3). 503-517 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Schoch OD, Schanz U, Koller M, Nakata K, Seymour JF, Russi EW, Boehler A: "Bronchoalveolar lavage findings in a patient with pulmonary alveolar proteinosis successfully treated with GM-CSF"Thorax. 57. 277-280 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Seymour JF, Doyle IR, Nakata K, Presneil IJ, AR Dunn: "Relationship of anti-GM-CSF antibody concentration, surfactant protein A and B levels, and serum LDH to pulmonary parameters and response to GM-CSF therapy in patients with idiopathic alveolar proteinosis"Thorax. 58. 252-257 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tranpnell B, whitsett J, Nakata K: "Pulmonary Alveolar Proteinosis ; Mechanism of Disease"New England Journal of Medicine. 349. 2528-2540 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中田 光(監修): "肺胞蛋白症の新展開"細胞. 34,第6号. 224-241 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中田 光, 内田寛治, 寺川貴裕, 慶長直人: "肺胞蛋白症の病因と抗GM-CSF自己抗体"呼吸器科. 1(1). 60-66 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中田 光: "突発性肺胞蛋白症の抗GM-CSF自己抗体をめぐる諸問題"Molecular Medicine. 39. 1398-1404 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中田 光: "肺胞蛋白症-最新の進歩"日本胸部臨床. 62. 197-203 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Uchida K, Nakata K, B.C.Trapnell, Terakawa T, Hamano E, Mikami A, Matsushita I, J.F.Seymour, Oh-eda M, Ishige I, Eishi Y, Kitamura T, Yamada Y, Hanaoka K, Keicho N: "High Affinity Autoantibodies Specifically Eliminate Granulocyte-Macrophage Colony-Stimulating Factor Activity In The Lungs Of Patients With Idiopathic Pulmonary Alveolar Proteinosis"Blood. 103. 1089-1098 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Du H-L, Ohtsuji M, Shigeta M, Chao DC, Sasaki K, Usuda Y, Yamada Y: "Expiratory asynchrony in proportional assist ventilation"Am.J.Respir.Crit.Care.Med.. 165. 972-977 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Du H-L, Amato MB, Yamada Y: "Closed-loop control of mechanical ventilation. (Automation of expiratory trigger sensitivity in pressure support ventilation)"Respir Care Clinics of North America. 7(3). 503-517 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Schoch GD, Schanz U, Koller M, Nakata K, Seymour JF, Russi EW, Boehier A: "Bronchoalveolar lavage findings in pulmonary alveolar proteinosis successfully treated with GM-CSF"Thorax. 57. 277-280 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Seymour JF, Doyle IR, Nakata K, Presneil U, AR Dunn: "Relationship of anti-GM-CSF antibody concentration, surfactant protein A and B levels, and LDH to pulmonary parameters and response to GM-CSF therapy in patientsn with idiopathic alveolar proteinosis"Thorax. 57. 252-257 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Trapnell B, Whitsett J, Nakata K: "Pulmonary Alveolar Proteinosis ; Mechanism of Disease"New England Journal of Medicine. 349. 2528-2540 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Uchida K: "High affinity autoantibodies specifically eliminate granulocyte-macrophage colony-stimulating factor activity in the lungs of patients with idiopathic pulmonary alveolar proteinosis"Blood. 103. 1089-1098 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 山田芳嗣: "ARDSの呼吸療法"Lisa別冊. 10. 94-101 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 山田宏: "ARDSモデル作成法"Surgery Frontier. 10(3). 295-299 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyashita T: "Spectral analyses of electroencephalography and heart rate variability during sleep in normal subjects. Autonomic Neuroscience"Basic and Clinical. 103. 114-120 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ogawa K: "Neural mechanism of propofol anesthesia in severe depression : A positron emission tomographic study"Anesthesiology. 98. 1101-1111 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishikawa Y: "A new technique for pulmonary arterial catheter insertion into coronary sinus using thransesophageal echocardiography"Anesth Analg. 97. 291-304 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中田 光, 内田寛治, 濱野栄美, 寺川貴裕, 慶長直人: "特発性肺胞蛋白症の抗GM-CSF自己抗体をめぐる諸問題.開け放たれたパンドラの箱"Molecular Medicine. 39(12). 1398-1404 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中田 光, 内田寛治, 寺川貴裕, 慶長直人: "肺胞蛋白症の病因と抗GM-CSF自己抗体"呼吸器科. 1(1). 60-66 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 内田寛治, 中田 光, 寺川貴裕, 慶長直人: "特発性肺胞蛋白症の成因と診断"呼吸. 21(7). 619-625 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中田 光: "肺胞蛋白症のブレークスルー:新しい治療・診断・病態解明へ向けて"細胞. 34(6). 224-225 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagayama H, Misawa K., Tanaka H, Ooi J, Iseki T, Tojo A, Tani K, Yamada Y, Kodo H., Takahashi TA, Yamashita N, Shimazaki S, Asano S.: "Transient hematopoietic stem cell rescue using umbilical cord blood for lethally irradiated nuclear accident victim"Bone Marrow Transplat. 29(3). 197-204 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Du H-L, Ohtsuji M, Shigeta M, Chao DC, Sasaki K, Usuda Y, Yamada Y: "Expiratory asynchrony in proportional assist ventilation"Am.J.Respir.Crit.Care.Med.. 165. 972-977 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagano O, Fujii H, Morimatsu H, Mizobuchi S, Goto K, Katayama H, Hirakawa M, Yamada Y.: "An adult with ARDS managed with high-frequency oscillatory ventilation and prone position"J Anesth. 16. 75-78 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 原田高志, 宮下徹也, 山田芳嗣: "症例検討「気管狭窄と麻酔管理」"Lisa. 9(8). 814-818 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 大塚将秀, 磨田裕, 山田芳嗣: "ARDS-呼吸管理法-"呼吸器科. 2(2). 116-121 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 山田芳嗣, 山口徹, 北原光夫 総編集: "今日の治療指針2002年度版 (機械的人工呼吸法 pp72-74)"医学書院. 1527 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 山田芳嗣, 丸川征四郎編集: "ナースの質問119 (人工呼吸器モニターを看護ケアに活かす pp193-195)"南光堂. 275 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 山田芳嗣, 丸川征四郎編集: "ナースの質問119 (PVカーブの読み方 pp196-198)"南光堂. 275 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 小出康弘, 山田芳嗣, 花岡一雄, 真下節, 福田和彦編集: "臨床麻酔学全書(上) (肺循環 pp54-74)"真興交易(株)医書出版部. 899 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Schoch OD: "BAL findings in a patient with pulmonary alvedar proteindsis successfury treated with GM-CSF"Thorax. 57・3. 277-280 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 内田 寛治: "サイトカインの自己抗体が起こす病体-特発性肺胞蛋白症-"最新医学. 56・6. 1254-1258 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 寺川 貴裕: "Surfactantの基本構造と病原微生物との結合、マグロファージ貧食"THE LUNG prespectives. 19・4. 458-461 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 中田 光: "特発性肺胞蛋白症と抗GM-CSF自己抗体"日本胸部臨床. 60sup. S93-S97 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 内田 寛治: "特発性肺胞蛋白症に対するサイトカイン大量療法の試み"臨床呼吸生理. 33・1. 11-13 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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