Elucidation of miRNA-mediated pathophysiology of MAC pulmonary disease

2018 Fiscal Year Annual Research Report

• Project/Area Number: 16K09941
• Research Institution: Keio University
• Principal Investigator: 長谷川 直樹 慶應義塾大学, 医学部(信濃町), 教授 (20198724)
• Co-Investigator(Kenkyū-buntansha): 星野 仁彦 国立感染症研究所, ハンセン病研究センター 感染制御部, 室長 (20569694) ; 西村 知泰 慶應義塾大学, 保健管理センター(日吉), 講師 (90348649)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 感染症

Outline of Annual Research Achievements

microRNA(miRNA)は、タンパク質をコードしない22塩基程度の1本鎖RNAであり、細胞内で転写調節因子として機能し、様々な疾患の病態に関与していることが近年報告されている。miRNAは細胞内で産生され細胞外に放出されるが、血液中にも存在しその測定も可能になってきた。
我々はこれまでに、肺Mycobacterium avium complex (MAC)症患者の血清でhsa-miR-346が有意に上昇し、肺MAC症の疾患活動性と血清hsa-miR-346濃度が相関していること、MAC感染ヒト末梢血単核球由来マクロファージ(ヒトマクロファージ)でhsa-miR-346分泌が亢進していることを確認した。更に前年度、結核菌感染ヒトマクロファージでもhsa-miR-346の分泌が亢進していることを確認した。そこで、肺結核症患者と健常者の血清hsa-miR-346濃度を比較したところ、肺結核症患者で、有意に血清hsa-miR-346濃度が上昇していた。以上より、hsa-miR-346が抗酸菌症の病態に関連し、抗酸菌症の疾患バイオマーカーになりうる可能性が示唆された。
ヒトマクロファージにMACや結核菌を感染させると、tumor necrosis factor (TNF)-αの分泌が亢進することを確認した。抗酸菌症の病態において、TNF-αは重要な役割を担っていることが報告されており、現在、抗酸菌症の病態におけるTNF-αとhsa-miR-346の関連性を検討している。

Research Products

• [Journal Article] Draft Genome Sequence of Mycolicibacterium sp. Strain NCC-Tsukiji, Isolated from Blood Culture of a Patient with Malignant Lymphoma (2019)
  • Author(s): Fukano H, Yoshida M, Shouji M, Hatta S, Maruyama D, Izutsu K, Shiotsuka M, Ogura Y, Hayashi T, Hasegawa N, Iwata S, Hoshino Y
  • Journal Title: Microbiology Resource Announcements Volume: 8 Pages: -
  • DOI: 10.1128/MRA.01575-18
  • Peer Reviewed / Open Access
• [Journal Article] Mycobacterium abscessus pulmonary disease: individual patient data meta-analysis (2019)
  • Author(s): Kwak N, Dalcolmo MP, Daley CL, Eather G, Gayoso R, Hasegawa N, Jhun BW, Koh WJ, Namkoong H, Park J, Thomson R, van Ingen J, Zweijpfenning SMH, Yim JJ
  • Journal Title: European Respiratory Journal Volume: - Pages: 1801991～1801991
  • DOI: 10.1183/13993003.01991-2018
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Efficacy and safety of intermittent maintenance therapy after successful treatment of Mycobacterium avium complex lung disease (2019)
  • Author(s): Asakura T, Nakagawa T, Suzuki S, Namkoong H, Morimoto K, Ishii M, Kurashima A, Betsuyaku T, Ogawa K, Hasegawa N
  • Journal Title: Journal of Infection and Chemotherapy Volume: 25 Pages: 218～221
  • DOI: 10.1016/j.jiac.2018.07.021
  • Peer Reviewed / Open Access
• [Journal Article] Development of lung cancer in patients with nontuberculous mycobacterial lung disease (2019)
  • Author(s): Kusumoto T, Asakura T, Suzuki S, Okamori S, Namkoong H, Fujiwara H,Yagi K, Kamata H, Ishii M, Betsuyaku T,Hasegawa N
  • Journal Title: Respiratory Investigation Volume: 57 Pages: 157～164
  • DOI: 10.1016/j.resinv.2018.11.004
  • Peer Reviewed / Open Access
• [Journal Article] First report of hepatobiliary Mycobacterium avium infection developing obstructive jaundice in a patient with neutralizing anti?interferon-gamma autoantibodies (2019)
  • Author(s): Namkoong H, Asakura T, Ishii M, Yoda S, Masaki K, Sakagami T, Iwasaki E, Yamagishi Y, Kanai T, Betsuyaku T, Hasegawa N
  • Journal Title: New Microbes and New Infections Volume: 27 Pages: 4～6
  • DOI: 10.1016/j.nmni.2018.10.001
  • Peer Reviewed / Open Access
• [Journal Article] Quantitative assessment of erector spinae muscles in patients with Mycobacterium avium complex lung disease (2018)
  • Author(s): Asakura T, Yamada Y, Suzuki S, Namkoong H, Okamori S, Kusumoto T, Niijima Y, Ozaki A, Hashimoto M, Yagi K, Kamata H, Funatsu Y, Ishii M, Jinzaki M, Betsuyaku T, Hasegawa N
  • Journal Title: Respiratory Medicine Volume: 145 Pages: 66～72
  • DOI: 10.1016/j.rmed.2018.10.023
  • Peer Reviewed / Open Access
• [Journal Article] Clinico-microbiological analysis of 121 patients with pulmonary Mycobacteroides abscessus complex disease in Japan ? An NTM-JRC study with RIT (2018)
  • Author(s): Morimoto K, Nakagawa T, Asami T, Morino E, Fujiwara H, Hase I, Tsujimoto Y, Izumi K, Hayashi Y, Matsuda S, Murase Y, Yano R, Takasaki J, Betsuyaku T, Aono A, Goto H, Nishimura T, Sasaki Y, Hoshino Y, Kurashima A, Ato M, Ogawa K, Hasegawa N, Mitarai S
  • Journal Title: Respiratory Medicine Volume: 145 Pages: 14～20
  • DOI: 10.1016/j.rmed.2018.10.012
  • Peer Reviewed / Open Access
• [Journal Article] Perfusion Defect?Concordant Progression of Unilateral Refractory Pulmonary Mycobacterium avium Complex Disease (2018)
  • Author(s): Asakura T, Yamada Y, Ishii M, Ebisudani T, Ueda S, Betsuyaku T, Hasegawa N
  • Journal Title: American Journal of Respiratory and Critical Care Medicine Volume: 198 Pages: 803～804
  • DOI: 10.1164/rccm.201801-0173IM
  • Peer Reviewed / Open Access
• [Journal Article] Amikacin Liposome Inhalation Suspension for Treatment-Refractory Lung Disease Caused by Mycobacterium avium Complex (CONVERT). A Prospective, Open-Label, Randomized Study (2018)
  • Author(s): Griffith DE, Eagle G, Thomson R, Aksamit TR, Hasegawa N, Morimoto K, Addrizzo-Harris DJ, O’Donnell AE, Marras TK, Flume PA, Loebinger MR, Morgan L, Codecasa LR, Hill AT, Ruoss SJ, Yim JJ, Ringshausen FC, Field SK, Philley JV, Wallace RJ, van Ingen J, Coulter C, Nezamis J, Winthrop KL
  • Journal Title: American Journal of Respiratory and Critical Care Medicine Volume: 198 Pages: 1559～1569
  • DOI: 10.1164/rccm.201807-1318OC
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association between six-minute walk test parameters and the health-related quality of life in patients with pulmonary Mycobacterium avium complex disease (2018)
  • Author(s): Yagi K, Asakura T, Namkoong H, Suzuki S, Asami T, Okamori S, Kusumoto T, Funatsu Y, Kamata H, Nishimura T, Ishii M, Betsuyaku T, Hasegawa N
  • Journal Title: BMC Pulmonary Medicine Volume: 18 Pages: -
  • DOI: 10.1186/s12890-018-0686-5
  • Peer Reviewed / Open Access
• [Journal Article] Mycobacterium triplex pulmonary disease with acquired macrolide resistance in immunocompetent patients (2018)
  • Author(s): Matsuda S, Suzuki S, Morimoto K, Aono A, Nishio K, Asakura T, Sasaki Y, Namkoong H, Nishimura T, Ogata H, Hasegawa N, Kurashima A, Ishii M, Tatsumi K, Mitarai S, Goto H
  • Journal Title: Clinical Microbiology and Infection Volume: 24 Pages: 671～672
  • DOI: 10.1016/j.cmi.2017.12.018
  • Peer Reviewed / Open Access
• [Journal Article] Health-related QOL of elderly patients with pulmonary M. avium complex disease in a university hospital (2018)
  • Author(s): Asakura T, Ishii M, Ishii K, Suzuki S, Namkoong H, Okamori S, Kamata H, Yagi K.、Funatsu Y.、Betsuyaku T.、Hasegawa N.
  • Journal Title: The International Journal of Tuberculosis and Lung Disease Volume: 22 Pages: 695～703
  • DOI: 10.5588/ijtld.17.0433
  • Peer Reviewed / Open Access
• [Journal Article] Epidemiology of Adults and Children Treated for Nontuberculous Mycobacterial Pulmonary Disease in Japan. (2018)
  • Author(s): Izumi K, Morimoto K, Hasegawa N, Uchimura K, Kawatsu L, Ato M, Mitarai S
  • Journal Title: Annals of the American Thoracic Society Volume: - Pages: -
  • DOI: 10.1513/AnnalsATS.201806-366OC
  • Peer Reviewed / Open Access
• [Presentation] 肺Mycobacterium avium complex(MAC)症における抗重力筋評価の意義. (2018)
  • Author(s): 朝倉崇徳, 山田祥岳, 鈴木翔二, 岡森慧, 楠本 竜也, 新島 友輝, 南宮 湖, 八木 一馬, 鎌田 浩史, 舩津 洋平, 石井 誠, 陣崎 雅弘, 別役 智子, 長谷川直樹
  • Organizer: 第58回日本呼吸器学会学術講演会
• [Presentation] 肺切除術を施行した肺非結核性抗酸菌(NTM)症の長予後の検討. (2018)
  • Author(s): 朝倉祟徳, 早川信祟, 長谷川直樹, 南宮湖, 竹内健, 鈴木翔二, 石井誠, 別役智子, 阿部能明, 大内基史
  • Organizer: 第58回日本呼吸器学会学術講演会
• [Presentation] ナショナルデータべースを用いた非結核性抗酸菌症の治療実態調査. (2018)
  • Author(s): 森本耕三, 泉清彦, 内村和広, 阿部学, 御手洗聡, 長谷川直樹
  • Organizer: 第58回日本呼吸器学会学術講演会
• [Presentation] アスペルギルス沈降抗体陽性である肺Mycobacterium avium complex症患者の臨床的特徴. (2018)
  • Author(s): 鈴木翔二, 朝倉崇徳, 南宮湖, 岡森慧, 八木一馬, 鎌田浩史, 舩津洋平, 中野奏, 西村知泰, 石井誠, 海老原全, 別役智子, 長谷川直樹
  • Organizer: 第58回日本呼吸器学会学術講演会
• [Presentation] 肺非結核性抗酸菌症に対するクラリスロマイシン,エサンブトール,リファンピシン3剤併用療法におけるPK/PD解析. (2018)
  • Author(s): 池谷修, 米屋安佳里, 松元一明, 榎木裕紀, 藤原宏, 上蓑義典, 宇野俊介, 長谷川直樹
  • Organizer: 第92回日本感染症学会学術講演会 第66回日本化学療法学会総会 合同学会
• [Presentation] 肺Mycobacterium avium complex症のフォローアップ中の肺癌合併患者の検討. (2018)
  • Author(s): 楠本竜也, 朝倉祟徳, 鈴木翔二, 岡森慧, 南宮湖, 藤原宏, 八木一馬, 鎌田浩史, 石井誠, 長谷川直樹
  • Organizer: 第93回日本結核病学会総会
• [Presentation] 肺Mycobacterium avium complex症に対する治療成功後の間欠的維持療法の効果と安全性に関する検討(多施設後ろ向き観察研究). (2018)
  • Author(s): 朝倉祟徳, 中川拓, 南宮湖, 鈴木翔二, 森本耕三, 石井誠, 倉島篤行, 小川賢二, 長谷川直樹
  • Organizer: 第93回日本結核病学会総会
• [Presentation] 肺Mycobacterium avium complex症に対する間欠的治療の検討(後ろ向き多施設共同研究). (2018)
  • Author(s): 中川拓, 朝倉祟徳, 森本耕三, 南宮湖, 鈴木翔二, 八木光昭, 福井保太, 林悠太, 垂水修, 山田憲隆, 星野仁彦, 倉島篤行, 長谷川直樹, 小川賢二
  • Organizer: 第93回日本結核病学会総会
• [Presentation] Analysis of Adverse Drug Events in Pulmonary Mycobacterium avium complex Disease Using the Japanese Adverse Drug Event Report (JADER) Database. (2018)
  • Author(s): Namkoong H, Takahashi Y, Ishii M, Asakura T, Suzuki S, Kamata H, Yagi K, Betsuyaku T, Matsumoto K, Kizu J, Hasegawa N
  • Organizer: International Conference of American Thoracic Society
  • Int'l Joint Research
• [Presentation] Randomized Phase 3 Trial of Amikacin Liposome Inhalation Suspension (ALIS) for Treatment-Refractory Nontuberculous Mycobacterial (NTM) Lung Disease Caused by Mycobacterium Avium Complex (MAC) in Adult Patients. (2018)
  • Author(s): DE Griffith, G Eagle, RM Thomson, TR Aksamit, Hasegawa N, Morimoto K, DJ Addrizzo-Harris, AE O’Donnell, TK Marras, PA Flume, MR Loebinger, LC Morgan, PF Castellotti, AT Hill, SJ Ruoss, JJ Yim, FC Ringshausen, SK Field, J Nezamis, KL Winthrop
  • Organizer: International Conference of American Thoracic Society
  • Int'l Joint Research
• [Presentation] Quantitative Assessment of Erector Spinae Muscles in Patients with Mycobacterium Avium Complex Lung Disease: Relationship of Disease Severity and Prognosis. (2018)
  • Author(s): Asakura T, Suzuki S, Okamori S, Kusumoto T, Namkoong H, Yagi K, Kamata H, Funatsu Y, Ishii M, Betsuyaku T, Hasegawa N
  • Organizer: International Conference of American Thoracic Society
  • Int'l Joint Research
• [Presentation] Six-Minute Walk Test (6MWT) Performance in Adult Patients Receiving Amikacin Liposome Inhalation Suspension (ALIS) for Treatment-Refractory Nontuberculous Mycobacterial (NTM) Lung Disease Caused by Mycobacterium Avium Complex (MAC). (2018)
  • Author(s): KL Winthrop, G Eagle, RM Thomson, TR Aksamit, Hasegawa N, Morimoto K, DJ Addrizzo-Harris, AE O'Donnell, TK Marras, PA Flume, MR Loebinger, LC Morgan, LR Codecasa, AT Hill, SJ Ruoss, JJ Yim, FC Ringshausen, SK Field, J Nezamis, DE Griffith
  • Organizer: International Conference of American Thoracic Society
  • Int'l Joint Research
• [Presentation] The Development of Lung Cancer During Follow-Up of Patients with Mycobacterium Avium Complex Lung Disease. (2018)
  • Author(s): Kusumoto T, Asakura T, Suzuki S, Okamori S, Namkoong H, Fujiwara H, Yagi K, Kamata H,Ishii M, Betsuyaku T, Hasegawa N
  • Organizer: International Conference of American Thoracic Society
  • Int'l Joint Research
• [Presentation] Patient-Reported Health Status Measured by St. George’s Respiratory Questionnaire Improved with Sputum Culture Conversion in Patients with Nontuberculous Mycobacterial (NTM) Lung Disease Caused by Mycobacterium Avium Complex (MAC). (2018)
  • Author(s): Winthrop K, Eagle G, Hasegawa N, Morimoto K, O'Donnell AE, Marras TK, Quittner AL, Chou E, Zhang R, Marcus J, Solem C, Deshpande CG, Lasch K, Nezamis J, Zhang Q
  • Organizer: International Conference of American Thoracic Society
  • Int'l Joint Research
• [Presentation] MIC distributions of 35 antibiotics for 54 clinical isolates of Mycobacterium lentiflavum. (2018)
  • Author(s): Takaki A, Aono A, Chikamatsu K, Igarashi Y, Yagi K, Asakura T, Hasegawa N, Matsuda S, Morimoto K, Sasaki Y, Ikeda M,Tomii T, Tamai K, Nakada Y, Murase Y, Yamada H,Mitarai S
  • Organizer: Annual Congress of European Respiratory Society
  • Int'l Joint Research
• [Presentation] Impact of six-minute walk test on health-related quality of life in pulmonary Mycobacterium avium complex disease. (2018)
  • Author(s): Yagi K, Asakura T, Namkoong H, Suzuki S, Asami T, Okamori S, Kusumoto T, Funatsu Y, Kamata H, Nishimura T, Ishii M, Betsuyaku T, Hasegawa N
  • Organizer: Annual Congress of European Respiratory Society
  • Int'l Joint Research
• [Presentation] Population based survey on the NTM pulmonary disease treatment in Japan. (2018)
  • Author(s): Izumi K, Morimoto K, Uchimura K, Ato M, Mitarai S, Hasegawa N
  • Organizer: Annual Congress of European Respiratory Society
  • Int'l Joint Research
• [Presentation] Actual treatment practices of pulmonary nontuberculous mycobacteriosis analysed from national insurance claim data in Japan. (2018)
  • Author(s): Morimoto K, Izumi K, Ato M, Mitarai S, Hasegawa N.
  • Organizer: Annual Congress of European Respiratory Society
  • Int'l Joint Research