Novel disease-specific autoantibodies of difuse interstitial lung diseases
Project/Area Number |
16K09537
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
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Research Institution | Osaka Toneyama Medical Center (2019) Osaka University (2016-2018) |
Principal Investigator |
Kida Hiroshi 独立行政法人国立病院機構大阪刀根山医療センター(臨床研究部), 独立行政法人国立病院機構大阪刀根山医療センター, 呼吸器内科部長 (80512988)
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Co-Investigator(Kenkyū-buntansha) |
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) |
2016-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 抗MX1抗体 / 抗GM-CSF抗体 / 蛋白アレイ / IPF / NSIP / 自己免疫性肺胞蛋白症 / 抗MX-1抗体 / REDCap / INSIP / 自己抗体 / IPAF / 抗ARS抗体 / ピルフェニドン / ニンテダニブ / IIPs / PAP / サルコイドーシス |
Outline of Final Research Achievements |
By the comprehensive analysis of serum autoantibodies among patients with chronic lung diseases using protein array, we found anti-MX1 antibody as idiopathic non-specific interstitial pneumonia (INSIP)-specific autoantibody. Similar to anti-ARS antibody, anti-MX1 antibody can cluster a sub-group of patients among chronic fibrosing idiopathic interstitial pneumonias. Both idiopathic pulmonary fibrosis (IPF) and INSIP-specific autoantibodies, which were identified by protein array, can mirror the lung pathology, therefore, possibly become, so called “non-invasive lung biopsy”. We established the method to clone variable region of B cell-receptor (BCR) gene, cluster the sequences of variable region of BCR, and produce monoclonal anti-GM-CSF antibodies derived from single peripheral monocytes in autoimmune pulmonary alveolar proteinosis patients. We also established the method to measure the function of these antibodies.
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Academic Significance and Societal Importance of the Research Achievements |
慢性線維化性間質性肺炎における抗MX1抗体発見は単に慢性線維化性特発性間質性肺炎を層別化するマーカーに止まらず、ウイルス感染と間質性肺炎の分子病態学的関係を解明する手がかりとなる。IPFとINSIPにおける疾患特異的自己抗体群は、肺病理を反映し、侵襲が大きい外科的肺生検に取って変わる、或いは補完する検査となる可能性がある。末梢血B細胞からモノクローナル自己抗体を作成、可変部領域の塩基配列データベースから構造予測に基づくクラスター解析、作成したモノクローナル抗体の機能解析を行う一連の手法は、自己抗体産生による自己免疫疾患全般の病態解析、有効な抗ウイルスワクチン開発に即応用可能である。
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Report
(5 results)
Research Products
(44 results)
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[Journal Article] Recombinant thrombomodulin for acute exacerbation in idiopathic interstitial pneumonias2019
Author(s)
Toru Arai, Hiroshi Kida, Yoshitaka Ogata, Satoshi Marumo, Hiroto Matsuoka, Iwao Gohma, Suguru Yamamoto, Masahide Mori, Chikatoshi Sugimoto, Kazunobu Tachibana, Masanori Akira, Ryuya Edahiro, Toshimitsu Hamasaki, Yoshikazu Inoue
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Journal Title
Respirology
Volume: 印刷中
Issue: 7
Pages: 658-666
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A lung abscess caused by secondary syphilis - the utility of polymerase chain reaction techniques in transbronchial biopsy: a case report.2019
Author(s)
Futami S, Takimoto T, Nakagami F, Satoh S, Hamaguchi M, Kuroyama M, Miyake K, Koyama S, Iwahori K, Hirata H, Nagatomo I, Takeda Y, Kida H, Kumanogoh A.
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Journal Title
BMC Infect Dis.
Volume: 19(1):598.
Issue: 1
Pages: 598-598
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Monitoring Antibody Binding to T Cells in a Pembrolizumab-Treated Patient With Lung Adenocarcinoma on Hemodialysis2019
Author(s)
Akio Osa, Takeshi Uenami, Yujiro Naito, Haruhiko Hirata, Shohei Koyama, Takayuki Takimoto, Takayuki Shiroyama, Shinji Futami, Saeko Nakatsubo, Nobuhiko Sawa, Yukihiro Yano, Izumi Nagatomo, Yoshito Takeda, Masahide Mori, Hiroshi Kida, Atsushi Kumanogoh
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Journal Title
Thorac Cancer
Volume: 11
Issue: 11
Pages: 2183-2187
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical implications of monitoring nivolumab immunokinetics in non?small cell lung cancer patients2018
Author(s)
Osa A, Uenami T, Koyama S, (22名飛ばして), Kida H, Akbay EA, Hammerman PS, Wong KK, Dranoff G, Mori M, Kijima T, Kumanogoh A
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Journal Title
JCI Insight
Volume: 3
Issue: 19
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] WT1 peptide-based immunotherapy for advanced thymic epithelial malignancies2018
Author(s)
Oji Y、Inoue M、Takeda Y、Hosen N、Shintani Y、Kawakami M、Harada T、Murakami Y、Iwai M、Fukuda M、Nishida S、Nakata J、Nakae Y、Takashima S、Shirakata T、Nakajima H、Hasegawa K、Kida H、Kijima T、Morimoto S、Fujiki F、Tsuboi A、Morii E、Morita S、Sakamoto J、Kumanogoh A、Oka Y、Okumura M、Sugiyama H
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Journal Title
International Journal of Cancer
Volume: 142
Issue: 11
Pages: 2375-2382
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Double deletion of tetraspanins CD9 and CD81 in mice leads to a syndrome resembling accelerated aging2018
Author(s)
Jin Y, Takeda Y, Kondo Y, Tripathi LP, Kang S, Takeshita H, Kuhara H, Maeda Y, Higashiguchi M, Miyake K, Morimura O、Koba T、Hayama Y、Koyama S、Nakanishi K、Iwasaki T、Tetsumoto Si、Tsujino K、Kuroyama M、Iwahori K、Hirata H、Takimoto Ti、Suzuki M、Nagatomo I、Sugimoto K、Fujii Y、Kida H、et al.
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Journal Title
Scientific Reports
Volume: 8
Issue: 1
Pages: 5145-5145
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A mouse model of Epstein-Barr virus LMP1 and LMP2A driven germinal center B-cell lymphoproliferative disease.2017
Author(s)
1Minamitani, T., Ma, Y., Zhou, H., Kida, H., Tsai, C.-Y., Obana, M., Okuzaki, D., Fujio, Y., Kumanogoh, A., Kikutani, H., Zhao, B., Kieff, E., Gewuz, B. E., Yasui, T.
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Journal Title
Proc. Natl. Acad. Sci. USA.
Volume: 印刷中
Issue: 18
Pages: 4751-4756
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Rapid intracranial response to osimertinib, without radiotherapy, in nonsmall cell lung cancer patients harboring the EGFR T790M mutation: Two Case Reports2017
Author(s)
Koba T, Kijima T, Takimoto T, Hirata H, Naito Y, Hamaguchi M, Otsuka T, Kuroyama M, Nagatomo I, Takeda Y, Kida H, Kumanogoh A
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Journal Title
Medicine (Baltimore)
Volume: 96
Issue: 6
Pages: 6087-6087
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Classification of idiopathic interstitial pneumonias using anti-myxovirus resistance-protein 1 autoantibody2017
Author(s)
Hamano Y, Kida H, Ihara S, Murakami A, Yanagawa M, Ueda K, Honda O, Tripathi LP, Arai T, Hirose M, Hamasaki T, Yano Y, Kimura T, Kato Y, Takamatsu H, Otsuka T, Minami T, Hirata H, Inoue K, Nagatomo I, Takeda Y, Mori M, Nishikawa H, Mizuguchi K, Kijima T, Kitaichi T, Tomiyama N, Inoue Y, Kumanogoh A
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Journal Title
Scientific Reports
Volume: 23
Issue: 1
Pages: 43201-43201
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Clarifying the biological significance of the CHK2 K373E somatic mutation discovered in The Cancer Genome Atlas database2016
Author(s)
Higashiguchi M, Nagatomo I, Kijima T, Morimura O, Miyake K, Minami T, Koyama S, Hirata H, Iwahori K, Takimoto T, Takeda Y, Kida H, Kumanogoh A
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Journal Title
FEBS letters
Volume: 590
Issue: 23
Pages: 4275-4286
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Prospective single arm open labeled multicenter trial for safety and efficacy of recombinant human thrombomodulin for acute exacerbation in idiopathic interstitial pneumonias (SETUP trial)2017
Author(s)
Arai T, Kida H, Ogata Y, Matumo S, Matsuoka H, Gohma I, Mori M, Yamamoto S, Sugimoto C, Tachibana K, Hamasaki T, Akira M, Inoue Y
Organizer
American Thoracic Society 2017
Related Report
Int'l Joint Research
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[Presentation] 当院におけるニボルマブ使用経験2016
Author(s)
長彰翁, 小山正平, 内藤祐二郎, 木庭太郎, 濱口眞成, 玄山宗到, 大塚倫之, 平田陽彦, 岩堀幸太, 滝本宜之, 長友泉, 武田吉人, 木田博, 熊ノ郷淳, 木島貴志
Organizer
第57回日本肺癌学会学術集会
Place of Presentation
福岡
Year and Date
2016-12-19
Related Report
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[Presentation] Establishment of the consecutive registration system for pulmonary alveolar proteinosis in Japan: Updated incidence, prevalence and surveillance for intractable cases2016
Author(s)
Inoue Y, Nakata K, Yamaguchi E, Arai T, Sugimoto C, Setoguchi Y, Ichiwata T, Ebina M, Cho K, Tazawa R, Ishii H, Kasai T, Akira M, Uchida K, Kida H, Homma S, Tatsumi K, Azuma A, Hagiwara K, Tomii K, Kitaichi M, Suzuki M, Morimoto K, Takada T, Nakayama H, Ohkouchi S, Tanaka T, Hirose M, Matsumuro A
Organizer
ERS International Congress 2016
Place of Presentation
London, UK
Year and Date
2016-09-03
Related Report
Int'l Joint Research
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[Presentation] Serum anti-myxovirus resistance protein-1 autoantibody; a possible novel biomarker for disease severity and prognosis of idiopathic pulmonary fibrosis2016
Author(s)
Arai T, Kida H, Hamano Y, Hirose M, Murakami A, Kagawa T, Matsumuro A, Koba T, Sugimoto C, Akira M, Kitaichi M, Ihara S, Kumanogoh A, Inoue Y
Organizer
American Thoracic Society Conference 2016
Place of Presentation
San Francisco, USA
Year and Date
2016-05-13
Related Report
Int'l Joint Research
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[Presentation] Autoantibody against GM-CSF presented by MHC class II in autoimmune pulmonary alveolar proteinosis2016
Author(s)
Hamano Y, Kida H, Hirose M, Matsumuro A, Suenaga T, Sarashina H, Hamasaki T, Inoue Y, Arase H, Kumanogoh A
Organizer
American Thoracic Society Conference 2016
Place of Presentation
San Francisco, USA
Year and Date
2016-05-13
Related Report
Int'l Joint Research
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[Presentation] 当院におけるニボルマブ使用経験2016
Author(s)
長彰翁, 小山正平, 二見悠, 菅泰彦, 内藤祐二郎, 石島見佳子, 木庭太郎, 濱口眞成, 玄山宗到, 大塚倫之, 平田陽彦, 岩堀幸太, 滝本宜之, 長友泉, 武田吉人, 木田博, 熊ノ郷淳, 木島貴志
Organizer
第104回日本肺癌学会関西支部会
Place of Presentation
大阪
Related Report
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