Identification and characterization of autoantibody against granulocyte-macrophage colony-stimulating factor in healthy individuals.

• Project/Area Number: 19390403
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: The University of Tokyo
• Principal Investigator: YAMADA Yoshitsugu The University of Tokyo, 医学部附属病院, 教授 (30166748)
• Co-Investigator(Kenkyū-buntansha): CHANG Kyungho 東京大学, 医学部附属病院, 講師 (50302708) ; KITAMURA Takayuki 東京大学, 医学部附属病院, 助教 (50302609) ; UCHIDA Kanji 東京大学, 医学部附属病院, 助教 (60302709)
• Project Period (FY): 2007 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000); Fiscal Year 2010: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2009: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2008: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2007: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• Keywords: 周術期管理学 / GM-CSF / 自己抗体 / 好中球機能 / 急性肺傷害 / SIRS / サイトカイン

Research Abstract

Autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) were reported by Nakata et al. in 1999. We detected low level of anti-GM-CSF autoantibody in serum from healthy individuals. It has neutralizing capacity and forms circulating immune complex in the serum, and may modulate myeloid cell immune functions. Anti-GM-CSF autoantibody may have a buffering effect to modulate GM-CSF bioactivity in vivo.

Research Products

• [Journal Article] Granulocyte/macrophage colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy persons. (2010)
  • Author(s): Uchida K, Carey B, Suzuki T, Nakata K, Trapnell B. Response
  • Journal Title: Blood. 14 ; 115(2) Pages: 431-3
• [Journal Article] Patient-derived granulocyte/macrophage colony-stimulating factor autoantibodies reproduce pulmonary alveolar proteinosis in nonhuman primates. (2010)
  • Author(s): Sakagami T, Beck D, Uchida K, Suzuki T, Carey BC, Nakata K, Keller G, Wood RE, Wert SE, Ikegami M, Whitsett JA, Luisetti M, Davies S, Krischer JP, Brody A, Ryckman F, Trapnell BC
  • Journal Title: Am J Respir Crit Care Med. 1 ; 182(1) Pages: 49-61
  • Peer Reviewed
• [Journal Article] High avidity cytokine autoantibodies in health and disease : pathogenesis and mechanisms. (2010)
  • Author(s): Watanabe M, Uchida K, Nakagaki K, Trapnell BC, Nakata K
  • Journal Title: Cytokine Growth Factor Rev. 21(4) Pages: 263-73
  • Peer Reviewed
• [Journal Article] High avidity cytokine autoantibodies in health and disease pathogenesis and mechanisms. (2010)
  • Author(s): Uchida K
  • Journal Title: Cytokine Growth Factor Rev. Volume: 21 Pages: 263-273
  • Peer Reviewed
• [Journal Article] Patient-derived granulocyte/macrophage colony-stimulating factor autoantibodies reproduce pulmonary alveolar proteinosis in nonhuman primates. (2010)
  • Author(s): Uchida K
  • Journal Title: Am J Respir Crit Care Med. Volume: 182 Pages: 49-61
  • Peer Reviewed
• [Journal Article] Response : Granulocyte/macrophage colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy persons (2010)
  • Author(s): Uchida K, Carey B, Suzuki T, Nakata K, Trapnell B.
  • Journal Title: Blood 115(2) Pages: 431-3
• [Journal Article] Granulocyte/macrophage-colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy subjects. (2009)
  • Author(s): Uchida K, Nakata K, Suzuki T, Luisetti M, Watanabe M, Koch DE, Stevens CA, Beck DC, Denson LA, Carey BC, Keicho N, Krischer JP, Yamada Y, Trapnell BC
  • Journal Title: Blood. 2 ; 113(11) Pages: 2547-56
  • Peer Reviewed
• [Journal Article] Granulocyte-macrophage colony-stimulating factor autoantibodies in murine ileitis and progressive ileal Crohn's disease. (2009)
  • Author(s): Han X, Uchida K, Jurickova I, Koch D, Willson T, Samson C, Bonkowski E, Trauernicht A, Kim MO, Tomer G, Dubinsky M, Plevy S, Kugathsan S, Trapnell BC, Denson LA
  • Journal Title: Gastroenterology. 136(4) Pages: 1261-71
  • Peer Reviewed
• [Journal Article] Pulmonary alveolar proteinosis, a primary immunodeficiency of impaired GM-CSF stimulation of macrophages. (2009)
  • Author(s): Trapnell BC, Carey BC, Uchida K, Suzuki T
  • Journal Title: Curr Opin Immunol. 21(5) Pages: 514-21
  • Peer Reviewed
• [Journal Article] Human GM-CSF autoantibodies and reproduction of pulmonary alveolar proteinosis. (2009)
  • Author(s): Sakagami T, Uchida K, Suzuki T, Carey BC, Wood RE, Wert SE, Whitsett JA, Trapnell BC, Luisetti M
  • Journal Title: N Engl J Med. 31 ; 361(27) Pages: 2679-81
  • Peer Reviewed
• [Journal Article] Human GM-CSF autoantibodies and reproduction of pulmonary alveolar proteinosis (2009)
  • Author(s): Sakagami T, Uchida K, Suzuki T, Carey BC, Wood RE, Wert SE, Whitsett JA, Trapnell BC, Luisetti M.
  • Journal Title: N Engl J Med. 361(27) Pages: 2679-81
• [Journal Article] Pulmonary alveolar proteinosis, a primary immunodeficiency of impaired GM-CSF stimulation of macrophages (2009)
  • Author(s): Trapnell BC, Carey BC, Uchida K, Suzuki T.
  • Journal Title: Curr Opin Immunol. 21(5) Pages: 514-21
• [Journal Article] Granulocyte-macrophage colony-stimulating factor autoantibodies in murine ileitis and progressive ileal Crohn's disease (2009)
  • Author(s): Han X, Uchida K, Jurickova I, Koch D, Willson T, Samson C, Bonkowski E, Trauernicht A, Kim MO, Tomer G, Dubinsky M, Plevy S, Kugathsan S, Trapnell BC, Denson LA.
  • Journal Title: Gastroenterology 136(4) Pages: 1261-71
• [Journal Article] Granulocyte/Macrophage Colony-Stimulating Factor Autoantibodies and Myeloid Cell Immune Funcitons in Healthy Subjects (2009)
  • Author(s): Uchida K, Nakata K, Suzuki T, Luisetti M, Watanabe M, Koch DE, Stevens CA, Beck DC, Denson LA, Carey BC, Keicho N, Krischer JP, Yamada Y, Trapnell BC.
  • Journal Title: Blood 113(11) Pages: 2547-56
• [Journal Article] Human GM-CSF autoantibodies and reproduction of pulmonary alveolar proteinosis (2009)
  • Author(s): Uchida K
  • Journal Title: New England Journal of Medicine 361 Pages: 2679-81
  • Peer Reviewed
• [Journal Article] Pulmonary alveolar proteinosis, a primary immunodeficiency of impaired GM-CSF stimulation of macrophages (2009)
  • Author(s): Uchida K
  • Journal Title: Current Opinion in Immunology 21 Pages: 514-21
  • Peer Reviewed
• [Journal Article] Granulocyte-macrophage colony-stimulating factor autoantibod ies in murine ileitis and progressive ileal Crohn's disease (2009)
  • Author(s): Uchida K
  • Journal Title: Gastroenterology 136 Pages: 1261-71
  • Peer Reviewed
• [Journal Article] Pulmonary alveolar proteinosis in Interstitial Lung Diseases (2009)
  • Author(s): Uchida K
  • Journal Title: European Respiratory Monograph Pages: 208-224
• [Journal Article] Graulocyte/Macrophage Co1Qhy-Stimulating Factor Autoantibodies and Myeloid Cell Immune Functions in Healthy Subjects. (2009)
  • Author(s): Uchida K
  • Journal Title: Blood 113(in press)
  • Peer Reviewed
• [Presentation] Meet the Professor Seminar ; MP401 : GM-CSF AUTOANTIBODY ; DISCOVERY, FUNCTIONS AND FUTURE APPLICATIONS. (2010)
  • Author(s): Uchida K, Nakata K
  • Organizer: American Thoracic Society Annual International Conference.
  • Place of Presentation: New Orleans, Louisiana, USA
  • Year and Date: 2010-05-16
• [Presentation] Meet the Professor Seminar; MP401 : GM-CSF AUTOANTIBODY; DISC OVERY, FUNCTIONS AND FUTURE APPLICATIONS (2010)
  • Author(s): Ucluda K
  • Organizer: American Thoracic Society Annual International Conference
  • Place of Presentation: New Orleans, Louisiana, USA
  • Year and Date: 2010-05-16
• [Presentation] 食道癌手術患者の侵襲に応じた好中球機能低下は術後早期回復に影響する (2009)
  • Author(s): 内田寛治、張京浩、山田芳嗣
  • Organizer: 日本麻酔科学会学術集会
  • Place of Presentation: 東京都
  • Year and Date: 2009-08-17
• [Presentation] 食道癌手術患者の侵襲に応じた好中球機能低下は術後早期回復に影響する (2009)
  • Author(s): 内田寛治, 室屋充明, 張京浩, 森和彦, 山田和彦, 瀬戸泰之, 伊藤伸子, 山田芳嗣
  • Organizer: 日本麻酔科学会第56回学術集会
  • Place of Presentation: 神戸市
  • Year and Date: 2009-08-17
• [Presentation] Reduced Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Bioactivity with Surgical Stress Associated with Early Postoperative Complications. (2009)
  • Author(s): 内田寛治, 張京浩, 山田芳嗣
  • Organizer: American Thoracic Society International Conference.
  • Place of Presentation: San Diego, USA
  • Year and Date: 2009-05-19
• [Presentation] Reduced Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Bioactivity with Surgical Stress Associated with Early Postoperative Complications (2009)
  • Author(s): Uchida K, Muroya M, Trapnell BC, Yamada K, Mori K, Seto Y, Yamada Y.
  • Organizer: American Thoracic Society International Conference
  • Place of Presentation: San Diego, USA
  • Year and Date: 2009-05-19
• [Presentation] Reduced Granulocyte-Macrophage Colony-Stimulating Factor(GM-CSF)Bioactivity with Surgical Stress Associated with Early Postoperative Complications (2009)
  • Author(s): 内田寛治、山田芳嗣
  • Organizer: American Thoracic Society International Conference
  • Place of Presentation: 米国、サンディエゴ
  • Year and Date: 2009-05-19
• [Presentation] Serologic Diagnosis of Pulmonary Alveolar Proteinosis (PAP). (2009)
  • Author(s): 内田寛治, 山田芳嗣
  • Organizer: American Thoracic Society International Conference.
  • Place of Presentation: San Diego, USA
  • Year and Date: 2009-05-18
• [Presentation] Serologic Diagnosis of Pulmonary Alveolar Proteinosis (PAP) (2009)
  • Author(s): Uchida K, Nakata K, Koch DE, Carey BC, Suzuki T, Stevens CA, Yamada Y, Trapnell BC.
  • Organizer: American Thoracic Society International Conference
  • Place of Presentation: San Diego, USA
  • Year and Date: 2009-05-18
• [Presentation] Serologic Diagnosis of Pulmonary Alveolar Proteinosis(PAP) (2009)
  • Author(s): 内田寛治、山田芳嗣
  • Organizer: American Thoracic Society International Conference
  • Place of Presentation: 米国、サンディエゴ
  • Year and Date: 2009-05-18
• [Presentation] ワークショップ3「基礎:炎症細胞の分離と機能的解析」「好中球」 (2008)
  • Author(s): 内田寛治
  • Organizer: 日本アレルギー学会秋季学術集会
  • Place of Presentation: 東京都
  • Year and Date: 2008-11-27
• [Presentation] ワークショップ3「基礎 : 炎症細胞の分離と機能的解析」「好中球」 (2008)
  • Author(s): 内田寛治
  • Organizer: 日本アレルギー学会第58回秋季学術集会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-27
• [Presentation] フローサイトメトリー法による簡易好中球活性化指標測定法の開発 (2008)
  • Author(s): 内田寛治、張京浩、山田芳嗣
  • Organizer: 日本麻酔科学会学術集会
  • Place of Presentation: 横浜市、神奈川県
  • Year and Date: 2008-06-12
• [Presentation] フローサイトメトリー法による簡易好中球活性化指標測定法の開発 (2008)
  • Author(s): 内田寛治, Trapnell BC, 張京浩, 山田芳嗣
  • Organizer: 日本麻酔科学会学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 2008-06-12
• [Presentation] A Standardized, Serum-Based Approach For Diagnosing PAP. (2008)
  • Author(s): 内田寛治
  • Organizer: American Thoracic Society International Conference
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2008-05-21
• [Presentation] A Stadardized, Serum-Based Approach For Diagnosing PAP (2008)
  • Author(s): Uchida K.
  • Organizer: American Thoracic Society International Conference
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2008-05-21
• [Presentation] A Standardized, Serum-Based ApProach For Diagnosing PAP (2008)
  • Author(s): 内田寛治
  • Organizer: Anlerican Thoracic Society International Conference
  • Place of Presentation: カナダ、トロント
  • Year and Date: 2008-05-21
• [Book] Pulmonary Alveolar Proteinosis in Interstitial Lung Diseases. (2009)
  • Author(s): Uchida K, Trapnell BC
  • Publisher: European Respiratory Monograph.
• [Book] European Respiratory Monograph (Issue 46)(edited by RON DU BOIS AND LUCA RICHELDI, Pulmonary alveolar proteinosis in Interstitial Lung Diseases) (2009)
  • Author(s): Trapnell BC, Uchida K
• [Remarks] ホームページ等