A study on the role and therapeutic application of B cell activation factor in autoimmune alveolar proteinosis

• Project/Area Number: 15K09203
• 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: Clinical Research Center, National Hospital Organization, Kinki-Chuo Chest Medical Center
• Principal Investigator: HIROSE MASAKI 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, 流動研究員 (90470195)
• 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)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 自己免疫性肺胞蛋白症 / 自己免疫性疾患 / B細胞

Outline of Final Research Achievements

We confirmed that B cell activation factors, BAFF and APRIL, were overproduced in the patients with autoimmune pulmonary alveolar proteinosis (APAP) in serum and bronchial alveolar lavage fluid compared to healthy subjects and other lung diseases. And we also confirmed that alveolar macrophages express BAFF and APRIL in the PAP lesion Immunohistochemically. As a result of overproduction of B cell activating factor, an increase in B cells was considered but a remarkable increase could not be confirmed.
Our results suggest that the need for multidisciplinary treatment such as total lung lavage, inhalation of GM-CSF, suppression of B cell activating factor is indicated for APAP treatment.

Research Products

• [Journal Article] A Semiquantitative Computed Tomographic Grading System for Evaluating Therapeutic Response in Pulmonary Alveolar Proteinosis (2017)
  • Author(s): Tokura Sayoko、Akira Masanori、Okuma Tomohisa、Tazawa Ryushi、Arai Toru、Sugimoto Chikatoshi、Matsumuro Akiko、Hirose Masaki et al.
  • Journal Title: Annals of the American Thoracic Society Volume: 14 Issue: 9 Pages: 1403-1411
  • DOI: 10.1513/annalsats.201607-574oc
  • Peer Reviewed
• [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] Risk factors for stomatitis in patients with lymphangioleiomyomatosis during treatment with sirolimus: A multicenter investigator-initiated prospective study. (2017)
  • Author(s): Kitamura N, Seyama K, Inoue Y, Nagai K, Suzuki M, Moriyama H, Takada T, Tazawa R, Hirai T, Mishima M, Hayashida M, Hirose M, Arai T, Sugimoto C, Hattori N, Watanabe K, Tamada T, Akazawa K, Tanaka T, Nakata K.
  • Journal Title: Pharmacoepidemiol Drug Saf. Volume: 26 Issue: 10 Pages: 1182-1189
  • DOI: 10.1002/pds.4259
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy and safety of transbronchial lung biopsy for the diagnosis of lymphangioleiomyomatosis: A report of 24 consecutive patients (2017)
  • Author(s): Koba Taro、Arai Toru、Kitaichi Masanori、Kasai Takahiko、Hirose Masaki、Tachibana Kazunobu、Sugimoto Chikatoshi、Akira Masanori、Hayashi Seiji、Inoue Yoshikazu
  • Journal Title: Respirology Volume: 23 Issue: 3 Pages: 331-338
  • DOI: 10.1111/resp.13190
  • Peer Reviewed
• [Journal Article] Efficacy and Safety of Long-Term Sirolimus Therapy for Asian Patients with Lymphangioleiomyomatosis (2016)
  • Author(s): Takada T, Mikami A, Kitamura N, Seyama K, Inoue Y, Nagai K, Suzuki M, Moriyama H, Akasaka K, Tazawa R, Hirai T, Mishima M, Hayashida M, Hirose M, Sugimoto C, Arai T, Hattori N, Watanabe K, Tamada T, Yoshizawa H, Akazawa K, Tanaka T, Yagi K, Young LR, McCormack FX, Nakata K
  • Journal Title: AnnalsATS Volume: 13 Issue: 11 Pages: 1912-1922
  • DOI: 10.1513/annalsats.201605-335oc
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A mathematical model to predict protein wash out kinetics during whole-lung lavage in autoimmune pulmonary alveolar proteinosis (2015)
  • Author(s): Keiichi Akasaka, Takahiro Tanaka, Takashi Maruyama, Nobutaka Kitamura, Atsushi Hashimoto, Yuko Ito, Hiroyoshi Watanabe, Tomoshige Wakayama, Takero Arai, Masachika Hayashi, Hiroshi Moriyama, Kanji Uchida, Shinya Ohkouchi, Ryushi Tazawa, Toshinori Takada, Etsuro Yamaguchi, Toshio Ichiwata, Masaki Hirose et al.
  • Journal Title: Am J Physiol Lung Cell Mol Physiol Volume: 14
  • Peer Reviewed
• [Journal Article] Outcome of corticosteroid administration in autoimmune pulmonary alveolar proteinosis: a retrospective cohort study (2015)
  • 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
  • Journal Title: BMC Pulmonary Medicine Volume: 15 Issue: 1 Pages: 88-88
  • DOI: 10.1186/s12890-015-0085-0
  • NAID: 120005758416
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 自己免疫性肺胞蛋白症におけるB細胞活性化因子 (2018)
  • Author(s): 広瀬雅樹、松室昭子、新井徹、 杉本親寿、審良正則、井上義一
  • Organizer: 第57回 日本呼吸器学会学術講演会
• [Presentation] 自己免疫性肺胞蛋白症おけるB細胞活性化因子 (2018)
  • Author(s): 広瀬 雅樹, 井上 義一
  • Organizer: 第16回 肺サーファクタント分子病態研究会
• [Presentation] B cell activating factors in patients with Autoimmune Pulmonary Alveolar Proteinosis (2018)
  • Author(s): Masaki Hirose, Akiko Matsumuro, Toru Arai, Chikatoshi Sugimoto, Masanori Akira, Kazunari Tsuyuguchi, Yoshinobu Matsuda, Maiko Naito, Yoshikazu Inoue
  • Organizer: American Thoracic Society
  • Int'l Joint Research
• [Presentation] 自己免疫性肺胞蛋白症の血清中におけるB細胞化性化因子 (2018)
  • Author(s): 広瀬 雅樹, 松室昭子, 新井徹, 杉本親寿, 井上義一
  • Organizer: 第71回国立病院総合医学会
• [Presentation] Increased concentration of B cell activating factors in the patients with Autoimmune Pulmonary Alveolar Proteinosis (2018)
  • Author(s): Masaki Hirose, Akiko Matsumuro, Toru Arai, Chikatoshi Sugimoto, Yoshikazu Inoue
  • Organizer: Asia Pacific Society of Respirology
  • Int'l Joint Research
• [Presentation] 自己免疫性肺胞蛋白症の血清中におけるB細胞活性化因子 (2017)
  • Author(s): 広瀬 雅樹, 松室昭子、新井徹、 杉本親寿、審良正則、井上義一
  • Organizer: 第56回日本呼吸器学会学術講演会
  • Place of Presentation: 京都
  • Year and Date: 2017-04-09
• [Presentation] Serum level of B cell activating factors in patients with Autoimmune Pulmonary Alveolar Proteinosis (2016)
  • Author(s): Masaki Hirose, Akiko Matsumuro, Toru Arai, Chikatoshi Sugimoto, Yoshikazu Inoue
  • Organizer: 21st Congress of APSR
  • Place of Presentation: Bangkok
  • Year and Date: 2016-11-24
  • Int'l Joint Research
• [Presentation] 自己免疫性肺胞蛋白症の血清中におけるB細胞活性化因子 (2016)
  • Author(s): 広瀬雅樹, 松室昭子, 杉本親寿, 新井徹, 井上義一
  • Organizer: 第52回 日本肺サーファクタント界面医学会
  • Place of Presentation: 金沢
  • Year and Date: 2016-10-29
• [Presentation] The elevation of BAFF and APRIL in patients with Autoimmune Pulmonary Alveolar Proteinosis (2016)
  • Author(s): Masaki Hirose, Akiko Matsumuro, Toru Arai, Chikatoshi Sugimoto, Yoshikazu Inoue
  • Organizer: Rare Lung Disease Consortium 2016
  • Place of Presentation: Kentucky
  • Year and Date: 2016-09-23
  • Int'l Joint Research
• [Presentation] 自己免疫性肺胞蛋白症の血清中におけるB細胞活性化因子 (2016)
  • Author(s): 広瀬 雅樹, 井上 義一
  • Organizer: 第15回 肺サーファクタント分子病態研究会
  • Place of Presentation: 札幌
  • Year and Date: 2016-06-04
• [Presentation] Increased concentration of BAFF and APRIL in patients with Autoimmune Pulmonary Alveolar Proteinosis (2016)
  • Author(s): Masaki Hirose, Akiko Matsumuro, Toru Arai, Chikatoshi Sugimoto, Masanori Akira, Yoshikazu Inoue
  • Organizer: ATS 2016 International Conference
  • Place of Presentation: San Francisco
  • Year and Date: 2016-05-15
  • Int'l Joint Research
• [Presentation] 自己免疫性肺胞蛋白症の血清中におけるB細胞活性化因子 (2016)
  • Author(s): 広瀬雅樹
  • Organizer: 第56回 日本呼吸器学会学術研究会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2016-04-09
• [Presentation] Serum B cell activating factors levels in patients with Autoimmune Pulmonary Alveolar Proteinosis (2015)
  • Author(s): Masaki Hirose
  • Organizer: American Thoracic Society
  • Place of Presentation: Colorado Convention Center
  • Year and Date: 2015-05-19
  • Int'l Joint Research
• [Presentation] 自己免疫性肺胞蛋白症の血清中におけるBAFF (2015)
  • Author(s): 広瀬雅樹
  • Organizer: 第55回 日本呼吸器学会学術研究会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2015-04-18
• [Book] 分子呼吸器病 (2018)
  • Author(s): 広瀬 雅樹, 井上 義一
  • Total Pages: 5
  • Publisher: 先端医学社
• [Book] 分子呼吸器病 (2017)
  • Author(s): 広瀬 雅樹, 井上 義一
  • Total Pages: 4
  • Publisher: 先端医学社
• [Book] 日本肺サーファクタント・界面医学会雑誌 (2017)
  • Author(s): 広瀬雅樹, 松室昭子, 杉本親寿, 新井徹, 井上義一
  • Total Pages: 1
  • Publisher: 日本肺サーファクタント・界面医学会
• [Book] 自己免疫性肺胞蛋白症の血清中におけるB細胞活性化因子 (2016)
  • Author(s): 広瀬雅樹, 井上義一
  • Total Pages: 4
  • Publisher: 先端医学社
• [Book] 呼吸 (2015)
  • Author(s): 広瀬雅樹
  • Total Pages: 14
  • Publisher: 一般財団法人 呼吸研究