Clinical significance of myositis-specific autoantibodies and novel biomarkers in polymyositis/dermatomyositis-associated interstitial lung disease

• Project/Area Number: 16K19449
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Hozumi Hironao 浜松医科大学, 医学部附属病院, 助教 (40771457)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 間質性肺疾患 / 皮膚筋炎 / 多発性筋炎 / YKL-40 / CD163 / 筋炎特異的抗体 / プロテオーム / 間質性肺炎 / キチナーゼ3様タンパク1 / バイオマーカー / 多発性筋炎/皮膚筋炎

Outline of Final Research Achievements

We explored novel biomarkers using bronchoalveolar lavage fluids and sera of patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD). The comprehensive analysis of serum myositis-specific autoantibodies suggested that the clinical features, treatment responses, and prognoses differed depending on MSA status, and therefore, therapeutic strategy should be considered according to MSA status. The shotgun proteomics using LC-MS/MS suggested that soluble CD163 and chitinase-3-like-1 (YKL-40) molecules may be candidate biomarkers for PM/DM-ILD. The validation analysis using the patients’ sera demonstrated that the two molecules were promising biomarkers for evaluating disease severity/activity and predicting prognosis.

Research Products

• [Journal Article] Anti-PL-7 Antisynthetase Syndrome with Eosinophilic Pleural Effusion (2018)
  • Author(s): Saito G, Kono M, Tsutsumi A, Koyanagi Y, Miyashita K, Kobayashi T, Hozumi H, Miki Y, Arai Y, Otsuki Y, Hashimoto D, Fujisawa T, Nakamura T, Suda T, Nakamura H.
  • Journal Title: Internal Medicine Volume: 57 Issue: 15 Pages: 2227-2232
  • DOI: 10.2169/internalmedicine.0302-17
  • NAID: 130007429162
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2018-08-01
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neutrophil gelatinase-associated lipocalin in patients with sarcoidosis. (2018)
  • Author(s): Kato S, Inui N, Hozumi H, Inoue Y, Yasui H, Karayama M, Kono M, Suzuki Y, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Watanabe H, Suda T.
  • Journal Title: Respiratory Medicine Volume: 印刷中 Pages: S20-S23
  • DOI: 10.1016/j.rmed.2018.01.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Distinctive characteristics and prognostic significance of interstitial pneumonia with autoimmune features in patients with chronic fibrosing interstitial pneumonia. (2018)
  • Author(s): Yoshimura K, Kono M, Enomoto Y, Nishimoto K, Oyama Y, Yasui H, Hozumi H, Karayama M, Suzuki Y, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Sumikawa H, Johkoh T, Colby TV, Sugimura H, Suda T.
  • Journal Title: Respiratory Medicine Volume: 137 Pages: 167-175
  • DOI: 10.1016/j.rmed.2018.02.024
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Respiratory impedance is correlated with airway narrowing in asthma using three-dimensional computed tomography (2018)
  • Author(s): Karayama M, Inui N, Mori K, Kono M, Hozumi H, Suzuki Y, Furuhashi K, Hashimoto D, Enomoto N, Fujisawa T, Nakamura Y, Watanabe H, Suda T.
  • Journal Title: Clin Exp Allergy Volume: 48 Issue: 3 Pages: 278-287
  • DOI: 10.1111/cea.13083
  • Peer Reviewed
• [Journal Article] Clinical Utility of YKL-40 in Polymyositis/dermatomyositis-associated Interstitial Lung Disease (2017)
  • Author(s): Hozumi H, Fujisawa T, Enomoto N, Nakashima R, Enomoto Y, Suzuki Y, Kono M, Karayama M, Furuhashi K, Murakami A, Inui N, Nakamura Y, Mimori T, Suda T
  • Journal Title: J Rheumatol Volume: 44 Issue: 9 Pages: 1394-1401
  • DOI: 10.3899/jrheum.170373
  • Peer Reviewed
• [Journal Article] Relationship between fraction of exhaled nitric oxide and airway morphology assessed by three-dimensional CT analysis in asthma (2017)
  • Author(s): Nishimoto K, Karayama M, Inui N, Mori K, Kono M, Hozumi H, Suzuki Y, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Watanabe H, Suda T
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 10187-10187
  • DOI: 10.1038/s41598-017-10504-w
  • Peer Reviewed / Open Access
• [Journal Article] Synchronous Duodenal Cancer and Lung Cancer Harboring an Epidermal Growth Factor Receptor Mutation Treated with Erlotinib and Oral Fluoropyrimidine (2017)
  • Author(s): Akiyama N, Karayama M, Iwaizumi M, Kusama Y, Kono M, Hozumi H, Suzuki Y, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Suda T.
  • Journal Title: Internal Medicine Volume: 56 Issue: 17 Pages: 2367-2371
  • DOI: 10.2169/internalmedicine.8312-16
  • NAID: 130006039389
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access
• [Journal Article] Radiologic pleuroparenchymal fibroelastosis-like lesion in connective tissue disease-related interstitial lung disease. (2017)
  • Author(s): Enomoto Y, Nakamura Y, Colby TV, Johkoh T, Sumikawa H, Nishimoto K, Yoshimura K, Matsushima S, Oyama Y, Hozumi H, Kono M, Fujisawa T, Enomoto N, Inui N, Iwashita T, Suda T.
  • Journal Title: PLoS One Volume: 12 Issue: 6 Pages: e0180283-e0180283
  • DOI: 10.1371/journal.pone.0180283
  • Peer Reviewed / Open Access
• [Journal Article] Type-1 polarised dendritic cells are a potent immunogen against Mycobacterium tuberculosis (2017)
  • Author(s): Satake Y.、Nakamura Y.、Kono M.、Hozumi H.、Nagata T.、Tsujimura K.、Enomoto N.、Fujisawa T.、Inui N.、Fujiyama T.、Tokura Y.、Matsui T.、Yokomura K.、Shirai M.、Hayakawa H.、Suda T.
  • Journal Title: The International Journal of Tuberculosis and Lung Disease Volume: 21 Issue: 5 Pages: 523-530
  • DOI: 10.5588/ijtld.16.0371
  • Peer Reviewed
• [Journal Article] Clinical diagnosis of idiopathic pleuroparenchymal fibroelastosis: A retrospective multicenter study. (2017)
  • Author(s): Enomoto Y, Nakamura Y, Satake Y, Sumikawa H, Johkoh T, Colby TV, Yasui H, Hozumi H, Karayama M, Suzuki Y, Furuhashi K, Fujisawa T, Enomoto N, Inui N, Iwashita T, Kuroishi S, Yokomura K, Koshimizu N, Toyoshima M, Imokawa S, Yamada T, Shirai T, Hayakawa H, Suda T.
  • Journal Title: Respir Med. Volume: 133 Pages: 1-5
  • DOI: 10.1016/j.rmed.2017.11.003
  • Peer Reviewed
• [Journal Article] Persistent impairment on spirometry in chronic eosinophilic pneumonia: a longitudinal observation study (Shizuoka-CEP study) (2017)
  • Author(s): Suzuki Y, Oyama Y, Hozumi H, Imokawa S, Toyoshima M, Yokomura K, Nakamura H, Kuroishi S, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Koshimizu N, Yamada T, Mori K, Masuda M, Shirai T, Hayakawa H, Sumikawa M, Johkoh T, Suda T
  • Journal Title: Ann Allergy Asthma Immunol Volume: 119 Issue: 5 Pages: 422-428
  • DOI: 10.1016/j.anai.2017.08.009
  • Peer Reviewed
• [Journal Article] Predictive factors for long-term outcome in polymyositis/dermatomyositis-associated interstitial lung diseases. (2017)
  • Author(s): Fujisawa T, Hozumi H, Kono M, Enomoto N, Nakamura Y, Inui N, Nakashima R, Imura Y, Mimori T, Suda T.
  • Journal Title: Respiratory Investigation Volume: 55 Issue: 2 Pages: 130-137
  • DOI: 10.1016/j.resinv.2016.09.006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical significance of soluble CD163 in polymyositis-related or dermatomyositis-related interstitial lung disease (2017)
  • Author(s): Enomoto Y, Suzuki Y, Hozumi H, Mori K, Kono M, Karayama M, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Inui N, Suzuki D, Ogawa N, Nakashima R, Mimori T, Iwashita T, Suda T
  • Journal Title: Arthritis Res Ther Volume: 19 Issue: 1 Pages: 9-9
  • DOI: 10.1186/s13075-016-1214-8
  • NAID: 120005973333
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Respiratory impedance is correlated with morphological changes in the lungs on three-dimensional CT in patients with COPD. (2017)
  • Author(s): Karayama M, Inui N, Mori K, Kono M, Hozumi H, Suzuki Y, Furuhashi K, Hashimoto D, Enomoto N, Fujisawa T, Nakamura Y, Watanabe H, Suda T.
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 41709-41709
  • DOI: 10.1038/srep41709
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comprehensive assessment of myositis-specific autoantibodies in polymyositis/ dermatomyositis- associated interstitial lung disease. (2016)
  • Author(s): Hozumi H, Fujisawa T, Nakashima R, Johkoh T, Sumikawa H, Murakami A, Enomoto N, Inui N, Nakamura Y, Hosono Y, Imura Y, Mimori T, Suda T
  • Journal Title: Respir Med. Volume: 121 Pages: 91-99
  • DOI: 10.1016/j.rmed.2016.10.019
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical Implication of Proteinase-3-antineutrophil Cytoplasmic Antibody in Patients with Idiopathic Interstitial Pneumonias. (2016)
  • Author(s): Hozumi H, Enomoto N, Oyama Y, Kono M, Fujisawa T, Inui N, Nakamura Y, Suda T.
  • Journal Title: Lung Volume: 194 Issue: 2 Pages: 235-242
  • DOI: 10.1007/s00408-016-9851-x
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Nonspecific interstitial pneumonia preceding diagnosis of collagen vascular disease. (2016)
  • Author(s): Kono M, Nakamura Y, Yoshimura K, Enomoto Y, Oyama Y, Hozumi H, Enomoto N,Fujisawa T, Inui N, Hamada E, Colby TV, Maekawa M, Suda T
  • Journal Title: Respir Med. Volume: 117 Pages: 40-47
  • DOI: 10.1016/j.rmed.2016.05.030
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Soluble hemoglobin scavenger receptor CD163 (sCD163) predicts mortality of community-acquired pneumonia (2016)
  • Author(s): Suzuki Y, Enomoto Y, Yokomura K, Hozumi H, Kono M, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Suda T
  • Journal Title: J Infect Volume: 73 Issue: 4 Pages: 375-377
  • DOI: 10.1016/j.jinf.2016.07.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Increased levels of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein in idiopathic pulmonary fibrosis. (2016)
  • Author(s): Kono M, Nakamura Y, Oyama Y, Mori K, Hozumi H, Karayama M, Hashimoto D, Enomoto N, Fujisawa T, Inui N, Yamada M, Hamada E, Colby TV, Maekawa M, Suda T
  • Journal Title: Respir Med. Volume: 115 Pages: 46-52
  • DOI: 10.1016/j.rmed.2016.04.013
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] YKL-40 Is a Useful Biomarker for Evaluating Disease Activity and Predicting Prognosis in Patients with Polymyositis/Dermatomyositis-Associated Interstitial Lung Disease. (2017)
  • Author(s): Hironao Hozumi, Tomoyuki Fujisawa, Masato Kono, Yuzo Suzuki, Masato Karayama, Kazuki Furuhashi, Noriyuki Enomoto, Naoki Inui, Yutaro Nakamura, Takafumi Suda.
  • Organizer: American Thoracic Society 2017 International Conference, 2017.
  • Int'l Joint Research
• [Presentation] 間質性肺疾患合併多発性筋炎/皮膚筋炎患者におけるキチナーゼ3様タンパク1の意義. (2017)
  • Author(s): 穗積宏尚, 河野雅人, 柄山正人, 鈴木勇三, 古橋一樹, 榎本紀之, 藤澤朋幸, 乾直輝, 中村祐太郎, 須田隆文.
  • Organizer: 第57回日本呼吸器学会学術講演会, 2017.
• [Presentation] 間質性肺炎を合併した多発性筋炎/皮膚筋炎患者におけるYKL-40の臨床的有用性の検討. (2017)
  • Author(s): 穗積宏尚, 河野雅人, 柄山正人, 鈴木勇三, 古橋一樹, 榎本紀之, 藤澤朋幸, 乾直輝, 中村祐太郎, 須田隆文.
  • Organizer: 第66回日本アレルギー学会学術大会, 2017.
• [Presentation] 間質性肺疾患を合併した多発性筋炎/皮膚筋炎患者における抗ARS抗体と抗MDA-5抗体測定の意義 (2016)
  • Author(s): 穗積宏尚
  • Organizer: 第65回日本アレルギー学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2016-06-17
• [Presentation] Serum anti-ARS and anti-MDA-5 antibodies are useful biomarkers for predicting the prognosis in patients with polymyositis/dermatomyositis-associated interstitial lung disease. (2016)
  • Author(s): Hozumi H, et al
  • Organizer: American Thoracic Society 2016 International Conference
  • Place of Presentation: San Francisco
  • Year and Date: 2016-05-19
  • Int'l Joint Research
• [Presentation] 多発性筋炎/皮膚筋炎に合併した間質性肺疾患患者における筋炎特異的抗体の意義 (2016)
  • Author(s): 穗積宏尚
  • 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