Investigation on molecular mechanism for progression of pulmonary alveolar proteinosis by next generation sequencing.
| Project/Area Number |
15H04829
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Niigata University |
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Principal Investigator |
Nakata Koh 新潟大学, 医歯学総合病院, 教授 (80207802)
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| Co-Investigator(Kenkyū-buntansha) |
坂上 拓郎 新潟大学, 医歯学総合病院, 講師 (00444159)
田澤 立之 新潟大学, 医歯学総合病院, 准教授 (70301041)
牛木 隆志 新潟大学, 医歯学総合病院, 講師 (80579152)
北村 信隆 新潟大学, 医歯学総合病院, 特任教授 (90224972)
井上 義一 独立行政法人国立病院機構近畿中央呼吸器センター, 臨床研究センター, 臨床研究センター長 (90240895)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2015: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
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| Keywords | 肺胞蛋白症 / 分子細胞呼吸器学 |
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| Outline of Final Research Achievements |
Autoimmune pulmonary alveolar proteinosis is caused by GM-CSF autoantibodies. We investigated the mechanism for polyclonality of the autoantibody and assessed the process for the clonal selection and expansion of autoreactive B cells against GM-CSF. We first generated bias-free full-length cDNA library from the circulating GM-CSF autoreactive B cells in ten patients, then amplified Ig specific PCR amplicons, and performed the deep sequencing. Most clones belonged to each one unique B cell lineage in one-to-one relationship. Somatic hyper mutation accounted for only up to 0.6% of the total. Thus, polyclonality of Igs in GM-CSF autoreactive B cell clones was mostly dependent on the variability of naive B cell clones.
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| Academic Significance and Societal Importance of the Research Achievements |
抗サイトカイン自己抗体が引き起こす疾患はいくつか知られているが、自己抗体濃度ばかりでなく、自己抗体の多様性が発症に重要であることがわかっている。我々は10人の自己免疫性肺胞蛋白症患者の末梢血B細胞より、自己抗体可変部のcDNA data baseを作成し、多様性の由来を調べた。その結果、重鎖、軽鎖ともに体細胞超変異はさかんに起こしているが、それが、クローンの多様性には繋がらず、クローンの多様性は、Naive B細胞の多様性に起因していることがわかった。自己免疫疾患の発症を解明する意味で重要な知見と思われた。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Elderly-onset hereditary pulmonary alveolar proteinosis and its cytokine profile.2017
Author(s)
Ito M, Nakagome K, Ohta H, Akasaka K, Uchida Y, Hashimoto A, Shiono A, Takada T, Nagata M, Tohyama J, Hagiwara K, Kanazawa M, Nakata K, Tazawa R.
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Journal Title
BMC Pulmonary Medicine.
Volume: 印刷中
Issue: 1
Pages: 40-40
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Sequential GM-CSF inhalation after whole lung lavage for pulmonary alveolar proteinosis: a report of five intractable cases.2017
Author(s)
Ohkouchi S, Akasaka K, Ichiwata T, Hisata S, Iijima H, Takada T, Tsukada H, Nakayama H, Machiya J, Irokawa T, Ogawa H, Shibata Y, Ichinose M, Ebina M, Nukiwa T, Kurosawa H, Nakata K, Tazawa R.
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Journal Title
Annals of American Thoracic Society.
Volume: 印刷中
Related Report
Peer Reviewed / Open Access
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[Journal Article] Outcome of corticosteroid administration in autoimmune pulmonary alveolar proteinosis: a retrospective cohort study2015
Author(s)
Keiichi Akasaka, Takahiro Tanaka, Nobutaka Kitamura, Shinya Ohkouchi, Ryushi Tazawa, Toshinori Takada, Toshio Ichiwata, Etsuro Yamaguchi, Masaki Hirose, Toru Arai, Kentaro Nakano, Takahito Nei, Haruyuki Ishii, Tomohiro Handa, Yoshikazu Inoue and Koh Nakata
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Journal Title
BMC Pulmonary Medicine
Volume: 15
Issue: 1
Pages: 88-88
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Possible Involvement of Lung Cells Harboring an2015
Author(s)
Moriyama M, Yano T, Furukawa T, Takada T, Ushiki T, Masuko M, Takizawa J, Sone H, Tazawa R, Saijo Y, Ishii H, Nakata K.
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Journal Title
Ann Am Thorac Soc.
Volume: 12
Pages: 1251-1253
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Elderly-Onset Hereditary Pulmonary Alveolar Proteinosis and CSF2RA Mutation.2016
Author(s)
Ito M,Nakagome K,Ohta H,Akasaka K,Uchida Y,Hashimoto A,Shiono A,Takada T,Nagata M,Tohyama J,Hagiwara K,Kanazawa M,Nakata K,Tazawa R
Organizer
American Thoracic Society International Conference2016
Place of Presentation
サンフランシスコ(アメリカ合衆国)
Related Report
Int'l Joint Research
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[Presentation] The Analysis of alveolar macrophage form on BALF specimens in secondary pulmonary alveolar proteinosis2015
Author(s)
H. Ishii, R. Tazawa, Y. Inoue, T. Saraya, T. Koide, T. Handa, M. Morita, S. Yamamoto, Y. Tanino, S. Ohkouchi, K. Tomii, K. Nakata
Organizer
American Thporacic Society International Conference 2015
Place of Presentation
コロラドコンベンションセンター（米国コロラド州デンバー市）
Year and Date
2015-05-19
Related Report
Int'l Joint Research
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