2003 Fiscal Year Final Research Report Summary
Development of a clinical method to assess disease severity and treatment effect in idiopathic pulmonary alveolar proteinosis
| Project/Area Number |
13671565
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Yokohama City University |
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Principal Investigator |
YAMADA Yoshitsugu Yokohama City University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (30166748)
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| 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)
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| Project Period (FY) |
2001 – 2003
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| Keywords | autoantibody / GM-CSF / idiopathic pulmonary alveolar proteinosis / epitope mapping / autoantibody titer / neutralizing activity / binding avidity and specificity / biochemical parameter |
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| 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.
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[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
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[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
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