The research on disease-specific autoantibodies in diffuse lung diseases

• Project/Area Number: 25461157
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Osaka University
• Principal Investigator: Kida Hiroshi 大阪大学, 医学系研究科, 助教 (80512988)
• Co-Investigator(Kenkyū-buntansha): 井上 義一 独立行政法人国立病院機構(近畿中央胸部疾患センター臨床研究センター), 臨床研究センター, 臨床研究センター長 (90240895)
• Research Collaborator: KUMANOGOH Atsushi
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: MX1 / INSIP / IPF / surgical lung biopsy / protein array / IIPs / diagnostic criteria / autoantibody / 自己抗体 / 蛋白アレイ / ARS / NSIP / 抗Mx1抗体 / 抗ARS抗体 / 抗NINJ2抗体 / サルコイドーシス / Mx1

Outline of Final Research Achievements

The current diagnostic criteria for idiopathic interstitial pneumonia (IIPs), which need surgical lung biopsy, sometimes forces patients a big burden. In addition, the diagnosis may change when the underlying diseases, such as collagen vasucular diseases, becomes apparent, during the follow-up period. In a trial to find disease-specific autoantibodies in idiopathic non-specific interstitial pneumonia (INSIP), we found anti-myxovirus resistance-protein 1 (MX1) autoantibody. The titer of anti-MX1 autoantibody elevated in about 17% of patients with chronic fibrosing IIPs. The positivity of anti-MX1 autoantibody was associated with better prognosis among patients with non-idiopathic pulmonary fibrosis (IPF). The current diagnostic criteria for IIPs must be complemented by molecular biomarker, such as the anti-MX1 autoantibody.

Research Products

• [Journal Article] Classification of idiopathic interstitial pneumonias using anti-myxovirus resistance-protein 1 autoantibody (2017)
  • 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
  • Journal Title: Scientific Reports Volume: 23 Issue: 1 Pages: 43201-43201
  • DOI: 10.1038/srep43201
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Rapid intracranial response to osimertinib, without radiotherapy, in nonsmall cell lung cancer patients harboring the EGFR T790M mutation: Two Case Reports (2017)
  • 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
  • Journal Title: Medicine (Baltimore) Volume: 96 Issue: 6 Pages: 6087-6087
  • DOI: 10.1097/md.0000000000006087
  • Peer Reviewed / Open Access
• [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.
  • Journal Title: Proc. Natl. Acad. Sci. USA. Volume: 印刷中 Issue: 18 Pages: 4751-4756
  • DOI: 10.1073/pnas.1701836114
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clarifying the biological significance of the CHK2 K373E somatic mutation discovered in The Cancer Genome Atlas database (2016)
  • 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
  • Journal Title: FEBS letters Volume: 590 Issue: 23 Pages: 4275-4286
  • DOI: 10.1002/1873-3468.12449
  • Peer Reviewed / Open Access
• [Journal Article] A retrospective study of prognostic factors in patients with interstitial pneumonia receiving long-term ocygen therapy (2014)
  • Author(s): Higashiguchi M, Kijima T, Sumikawa H, Honda O, Minami T, Hirata H, Inoue K, Nagatomo I, Takeda Y, Kida H, Tomiyama N, Kumanogoh A.
  • Journal Title: Lung Volume: 192 Issue: 5 Pages: 729-737
  • DOI: 10.1007/s00408-014-9623-4
  • Peer Reviewed / Open Access
• [Journal Article] Development of microscopic polyangiitis-related pulmonary fibrosis in a patient with autoimmune pulmonary alveolar proteinosis (2014)
  • Author(s): Kinehara Y, Kida H, Inoue Y, Hirose M, Nakabayashi A, Takeuchi Y, Hayama Y, Fukushima K, Hirata H, Inoue K, Minami T, Nagatomo I, Takeda Y, Funakoshi T, Kijima T, Kumanogoh A
  • Journal Title: BMC Pulm Med Volume: 14 Issue: 1 Pages: 172-172
  • DOI: 10.1186/1471-2466-14-172
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 早期に評価できたオシメルチニブの脳転移奏効2症例 (2017)
  • Author(s): 岡森仁臣、木庭太郎、平田陽彦、内藤祐二朗、濱口眞成、大塚倫之、玄山宗到、長友泉、武田吉人、木田博、木島貴志、熊ノ郷淳
  • Organizer: 第105回肺癌学会関西支部会
  • Place of Presentation: 大阪
• [Presentation] コバスv2法でT790M陰性腫瘤がオシメルチニブにより縮小した肺腺癌の一例 (2017)
  • Author(s): 木庭太郎、平田陽彦、内藤祐二朗、濱口眞成、大塚倫之、玄山宗到、長友泉、武田吉人、木田博、木島貴志、熊ノ郷淳
  • Organizer: 第105回肺癌学会関西支部会
  • Place of Presentation: 大阪
• [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
• [Presentation] Anti-GM-CSF/HLA class II complex autoantibody in autoimmune pulmonary alveolar proteinosis (2016)
  • Author(s): Kida H, Hamano Y, Hirose M, Suenaga T, Sarashina H, Inoue Y, Arase H, Kumanogoh A
  • Organizer: Asian Pacific Society Respirology Congress 2016
  • Place of Presentation: Bangkok,Thai
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Establishment of the consecutive registration system for pulmonary alveolar proteinosis in Japan: Updated incidence, prevalence and surveillance for intractable cases (2016)
  • 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
  • Int'l Joint Research
• [Presentation] 自己免疫性肺胞蛋白症における抗GM-CSF/HLA class II複合体抗体の意義 (2016)
  • Author(s): 木田 博，濱野芳匡、熊ノ郷淳、井上義一、末永忠広、荒瀬尚
  • Organizer: 第2回日本骨免疫学会
  • Place of Presentation: 沖縄
  • Year and Date: 2016-07-06
• [Presentation] Serum anti-myxovirus resistance protein-1 autoantibody; a possible novel biomarker for disease severity and prognosis of idiopathic pulmonary fibrosis (2016)
  • 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
  • Int'l Joint Research
• [Presentation] Autoantibody against GM-CSF presented by MHC class II in autoimmune pulmonary alveolar proteinosis (2016)
  • 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
  • Int'l Joint Research
• [Presentation] 自己免疫性肺胞蛋白症における抗GM-CSF/HLA class II複合体抗体の意義 (2016)
  • Author(s): 濱野芳匡、木田博、熊ノ郷淳、井上義一、Yan Jiang、荒瀬尚
  • Organizer: 第56回日本呼吸器学会学術講演会
  • Place of Presentation: 京都
  • Year and Date: 2016-04-08
• [Presentation] 呼気中揮発性有機化合物プロファイリングシステムに基づくEGFR-TKI投薬効果評価法の開発 (2016)
  • Author(s): 藤本浩史、木田博、森雅秀、矢野幸洋、立花功、藤村耕治、福崎英一郎、馬場健史
  • Organizer: 第56回日本呼吸器学会学術講演会
  • Place of Presentation: 京都
  • Year and Date: 2016-04-08
• [Presentation] 外陰部Paget病の経過中にPulmonary tumor thrombotic microangiopathyを発症した1例 (2016)
  • Author(s): 三好 毅，二見 悠，大塚倫之，平田陽彦，小山正平，長友 泉，武田吉人，木田 博，木島貴志，熊ノ郷淳
  • Organizer: 第212回日本内科学会近畿地方会
  • Place of Presentation: 大阪
• [Presentation] 閉塞性細気管支炎を合併した腫瘍随伴性天疱瘡と考えられた一例 (2016)
  • Author(s): 白石万紀子、東口将佳、滝本宜之、武田吉人、木庭太郎、濱口眞成、内藤祐二朗、玄山宗到、大塚倫之、中西香織、岩堀幸太、平田陽彦、小山正平、長友泉、木田博、木島 貴志
  • Organizer: 第87回日本呼吸器学会近畿地方会
  • Place of Presentation: 大阪
• [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
• [Presentation] 当院におけるLAM診療の現状と展望 (2016)
  • Author(s): 滝本宜之、平田陽彦、玄山宗到、武田吉人、木田博、木島貴志、熊ノ郷淳
  • Organizer: 第1回 LAM研究会
  • Place of Presentation: 東京
• [Presentation] Reversed halo signを呈し気管支鏡にて肺接合菌症と診断した２症例 (2016)
  • Author(s): 内藤祐二朗、平田陽彦、玄山宗到、木庭太郎、濱口眞成、大塚倫之、長友泉、武田吉人、木田博、木島貴志、熊ノ郷淳
  • Organizer: 第88回 日本呼吸器学会学近畿地方会
  • Place of Presentation: 京都
• [Presentation] ニボルマブの薬剤性肺障害に対するステロイド加療中に発症し、肺障害再燃との鑑別を要した肺MAC症の一例 (2016)
  • Author(s): 木庭太郎、平田陽彦、長友泉、内藤祐二朗、濱口眞成、玄山宗到、大塚倫之、武田吉人、木田博、木島貴志、熊ノ郷淳
  • Organizer: 第88回 日本呼吸器学会学近畿地方会
  • Place of Presentation: 京都
• [Presentation] 慢性特発性間質性肺炎におけるフェノタイプ分類及び自己免疫性肺胞蛋白症における重症度バイオマーカーに関わる自己抗体研究 (2015)
  • Author(s): 濱野芳匡、木田博、熊ノ郷淳、梁川雅弘、上田賢、本多修、井上義一、Yan Jiang、荒瀬尚、村上昭弘
  • Organizer: 第24回PneumoForum
  • Place of Presentation: 東京
  • Year and Date: 2015-11-07
• [Presentation] 慢性特発性間質性肺炎の新たなentityを形成する抗Mx1自己抗体の意義 (2015)
  • Author(s): 濱野芳匡、木田博、熊ノ郷淳、広瀬雅樹、井上義一
  • Organizer: 第43回日本臨床免疫学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-10-22
• [Presentation] 間質性肺炎における抗Mx1自己抗体の意義 (2015)
  • Author(s): 濱野芳匡、木田博、熊ノ郷淳、梁川雅弘、上田賢、本多修、広瀬雅樹、井上義一、村上昭弘
  • Organizer: 第18回間質性肺炎細胞分子病態研究会
  • Place of Presentation: 東京
  • Year and Date: 2015-08-22
• [Presentation] 特発性非特異的間質性肺炎（Idiopathic NSIP）における疾患特異的自己抗体検索
  • Author(s): 濱野芳匡、木田博、森島淳仁、平野亨、楢崎雅司、嶋良仁、緒方篤、立花功、田中敏郎、熊ノ郷淳
  • Organizer: 第57回日本リウマチ学会総会・学術集会
  • Place of Presentation: 京都市
• [Presentation] 特発性非特異的間質性肺炎における疾患特異的自己抗体の検索
  • Author(s): 木田博
  • Organizer: 第16回間質性肺炎細胞分子病態研究会
  • Place of Presentation: 東京
• [Presentation] 特発性非特異的間質性肺炎診断における抗Mx1抗体の有用性
  • Author(s): 濱野芳匡、木田博、森島淳仁、平野亨、楢崎雅司、嶋良仁、緒方篤、立花功、田中敏郎、熊ノ郷淳
  • Organizer: 第58回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] 網羅的自己抗体検索によるINSIP特異的マーカー、抗Mx1抗体の同定
  • Author(s): 木田博、濱野芳匡、井原祥一、井上義一、新井徹、広瀬雅樹、矢野幸洋、森雅秀、南俊行、平田陽彦、長友泉、井上幸治、武田吉人、木島貴志、熊ノ郷淳
  • Organizer: 第54回日本呼吸器学会学術講演会
  • Place of Presentation: 大阪
• [Presentation] Identification of anti-myxovirus resistance protein-1 autoantibody as a specific marker for idiopathic nonspecific interstitial pneumonia
  • Author(s): Yoshimasa Hamano, Hiroshi Kida, Shoichi Ihara, Hiroyoshi Nishikawa, Toru Arai, Masaki Hirose, Lokesh P. Tripathi, Tetsuya Kimura, Yasuko Tada, Yukihiro Yano, Masahide Mori, Kenji Mizuguchi, Shimon Sakaguchi, Yoshikazu Inoue, Atsushi Kumanogoh
  • Organizer: ATS international conference 2014
  • Place of Presentation: San Diego, CA,U.S.A.
• [Patent(Industrial Property Rights)] 非特異的間質性肺炎の診断のためのバイオマーカー (2014)
  • Inventor(s): 木田博、熊ノ郷淳、荒瀬尚、井上義一
  • Industrial Property Rights Holder: 木田博、熊ノ郷淳、荒瀬尚、井上義一
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-03-17
  • Overseas