Clarification of the mechanism of the chronicity of allergic diseases and establishment of the thrapeutic strategy against it

2016 Fiscal Year Annual Research Report

• Project/Area Number: 16H05343
• Research Institution: Saga University
• Principal Investigator: 出原 賢治 佐賀大学, 医学部, 教授 (00270463)
• Co-Investigator(Kenkyū-buntansha): 南里 康弘 (宮内康弘) 佐賀大学, 医学部, 特別研究員 (00382218) ; 太田 昭一郎 佐賀大学, 医学部, 研究講師 (20346886) ; 布村 聡 佐賀大学, 医学部, 助教 (70424728) ; 小川 雅弘 佐賀大学, 医学部, 助教 (90599317)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ペリオスチン / 特発性肺線維症 / バイオマーカー

Outline of Annual Research Achievements

血清中のペリオスチンの性質について検討した。その結果、血清ペリオスチンの多くは非還元状態では高い分子量を持った多量体として存在し、一部が単量体として存在することが明らかとなった。還元状態では多量体は単量体となることから、分子間ジスルフィド結合により多量体は形成されていると考えられた。単量体を特異的に認識する抗体を取得し、血清での単量体ペリオスチン測定を行った。その結果、特発性肺線維症(IPF)患者において単量体ペリオスチンが上昇しており、IPFの診断において単量体ペリオスチンはKL-6やSP-Dと同等の性能を示し、IPFの予後予測（6ヵ月後の呼吸機能低下）においては、単量体ペリオスチンはKL-6やSP-Dより優れた性能を示した。さらに、総ペリオスチンにおける単量体ペリオスチンの割合は、喘息、アトピー性皮膚炎、強皮症に比べてIPFにおいて高くなっていた。以上より、IPF患者においては単量体ペリオスチンの産生が亢進しており、単量体ペリオスチンの測定がIPFの診断、あるいは予後予測において有用であることが明らかとなった。IPFはヘテロな病態からなる疾患であると考えられており、その予後を予測することは、内科治療の適用、肺移植の早期適用を判断する上で重要となっている。現在、企業との共同開発により単量体ペリオスチンを測定するための診断薬開発を進めており、今後IPFの診断・治療を進める上で有用となると期待される。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

今年度すでに単量体ペリオスチンを特異的に検出するELISAシステムを構築し、IPFの診療における有用性を示すことができた。

Strategy for Future Research Activity

当初の目標通り、ペリオスチンのシグナル伝達に関する解析を進めるとともに、ペリオスチンとインテグリンの結合を阻害する物質の検討を進め、ペリオスチンが関与する疾患を標的とした創薬の開発につなげる。

Research Products

• [Journal Article] Reduced vitreal concentration of periostin after vitrectomy in patients with proliferative diabetic retinopathy (2016)
  • Author(s): Tachibana T, Yoshida S, Kobayashi Y, Nakama T, Ishikawa K, Nakao S, Izuhara K, Kono T, Ishibashi T
  • Journal Title: Acta Ophthalmologica Volume: 94 Pages: e81-e82
  • DOI: 10.1111/aos.12752
  • Peer Reviewed / Open Access
• [Journal Article] Increased YKL-40 and chitotriosidase in asthma and chronic obstructive pulmonary disease (2016)
  • Author(s): James AJ, Reinius LE, Verhoek M, Gomes A, Kupczyk M, Hammar U, Ono J, Ohta S, Izuhara K, Bel E, Kere J, Söderhäll C, Dahlén B, Boot RG, Dahlén S
  • Journal Title: American Journal of Respiratory and Critical Care Medicine Volume: 193 Pages: 131-142
  • DOI: 10.1164/rccm.201504-0760OC
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Roles of periostin in respiratory disorders (2016)
  • Author(s): Izuhara K, Conway SJ, Moore BB, Matsumoto H, Holweg CTJ, Matthews JG, Arron JR
  • Journal Title: American Journal of Respiratory and Critical Care Medicine Volume: 193 Pages: 949-956
  • DOI: 10.1164/rccm.201510-2032PP
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Elevation of serum squamous cell carcinoma antigen 2 in patients with psoriasis: associations with disease severity and response to the treatment (2016)
  • Author(s): Watanabe Y, Yamaguchi Y, Komitsu N, Ohta S, Azuma Y, Izuhara K, Aihara M
  • Journal Title: British Journal of Dermatology Volume: 174 Pages: 1327-1336
  • DOI: 10.1111/bjd.14426
  • Peer Reviewed / Open Access
• [Journal Article] Periostin and Interleukin-13 Are Independently Related to Chronic Spontaneous Urticaria (2016)
  • Author(s): Bae Y, Izuhara K, Ohta S, Ono J, Hong GU, Ro JY, Park GH, Choi JH
  • Journal Title: Allergy, Asthma & Immunology Research Volume: 8 Pages: 457-460
  • DOI: 10.4168/aair.2016.8.5.457.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Multidimensional endotyping in severe asthma reveals inflammatory heterogeneity in MMPs and YKL-40 (2016)
  • Author(s): Hinks T, Brown T, Lau LCK, Rupani H, Barber C, Elliott S, Ward JA, Ono J, Ohta S, Izuhara K, Djukanovi; R, Kurukulaaratchy R, Chauhan A, Howarth PH
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 138 Pages: 61-75
  • DOI: 10.1016/j.jaci.2015.11.020
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The usefulness of measuring tear periostin for the diagnosis and management of ocular allergic diseases (2016)
  • Author(s): Fujishima H, Okada N, Matsumoto K, Fukagawa K, Igarashi A, Matsuda A, Ono J, Ohta S, Mukai H, Yoshikawa M, Izuhara K
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 138 Pages: 459-467
  • DOI: 10.1016/j.jaci.2015.11.039
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Using periostin as a biomarker in the treatment of asthma (2016)
  • Author(s): Izuhara K, Ohta S, Ono S
  • Journal Title: Allergy, Asthma and Immunology Research Volume: 8 Pages: 491-498
  • DOI: 10.4168/aair.2016.8.6.491
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Allergen immunotherapy for allergic asthma: protocol for a systematic review (2016)
  • Author(s): Dhami S, Nurmatov U, Agache I, Lau S, Muraro A, Jutel M, Roberts G, Akdis C, Bonini M, Calderon M, Casale T, Cavkaytar O, Cox L, Demoly P, Flood B, Hamelmann E, Izuhara K
  • Journal Title: Clinical and Translational Allergy Volume: 6 Pages: 5
  • DOI: 10.1186/s13601-016-0094-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Periostin as a biomarker for diagnosis of pediatric asthma (2016)
  • Author(s): Inoue T, Akashi K, Watanabe M, Ikeda Y, Ashizuka S, Motoki T, Suzuki R, Sagara N, Yanagida N, Sato S, Ebisawa M, Ohta S, Ono J, Izuhara K, Katunuma T
  • Journal Title: Pediatric Allergy and Immunology Volume: 27 Pages: 521-526
  • DOI: 10.1111/pai.12575
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Serum periostin and free IgE levels in the responsiveness to omalizumab in patients with severe asthma (2016)
  • Author(s): Tajiri T, Matsumoto H, Gon Y, Ito R, Hashimoto S, Izuhara K, Suzukawa M, Ohta K, Ono J, Ito I, Oguma T, Inoue H, Iwata T, Nagasaki T, Kanemitsu T, Niimi A, Mishima M
  • Journal Title: Allergy Volume: 71 Pages: 1472-1479
  • DOI: 10.1111/all.12922
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clinical implication of the serum periostin level for differentiating phenotypes of NSAID hypersensitivity (2016)
  • Author(s): Kim M, Yoon MK, Lee Y-S, Izuhara K, Ohta S, Ono J, Kim J-H, Ban GY, Ye Y-M, Park H-S
  • Journal Title: Allergology International Volume: 65 Pages: 492-494
  • DOI: 10.1016/j.alit.2016.04.013
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The potential for repositioning anti-thyroid agents as anti-asthma drugs (2016)
  • Author(s): Suzuki S, Ogawa M, Ohta S, Arima K, Nunomura S, Nanri Y, Mitamura Y, Yoshihara T, Nakamura Y, Yamauchi K, Chibana K, Ishii Y, Lee JJ, Aratani Y, Kakuta S, Kubo S, Iwakura Y, Yoshida H, Izuhara K
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 138 Pages: 1458-1461
  • DOI: 10.1016/j.jaci.2016.04.047
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Periostin promotes hepatic fibrosis in mice by modulating hepatic stellate cell activation via αv integrin interaction (2016)
  • Author(s): Sugiyama A, Kanno K, Nishimichi N, Ohta S, Ono J, Conway SJ, Izuhara K, Yokosaki Y, Tazuma S
  • Journal Title: Journal of Gastroenterology Volume: 51 Pages: 1161-1174
  • DOI: 10.1007/s00535-016-1206-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Induction of airway allergic inflammation by hypothiocyanite via epithelial cells (2016)
  • Author(s): Suzuki S, Ogawa M, Ohta S, Nunomura S, Nanri Y, Shiraishi H, Mitamura Y, Yoshihara T, James J. Lee, Izuhara K
  • Journal Title: Journal of Biological Chemistry Volume: 291 Pages: 27219-27227
  • DOI: 10.1074/jbc.M116.746909
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 新規治療薬のコンパニオン診断 (2016)
  • Author(s): 出原賢治
  • Organizer: 第3回日本アレルギー学会総合アレルギー講習会
  • Place of Presentation: 横浜
  • Year and Date: 2016-12-17
  • Invited
• [Presentation] アレルギー疾患とペリオスチン (2016)
  • Author(s): 出原賢治
  • 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: 2016-06-19
  • Invited
• [Presentation] Allergology Internationalから観た英文論文作製の注意点とコツ (2016)
  • Author(s): 出原賢治
  • 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
  • Invited
• [Presentation] The potential for repositioning anti-thyroid agents as anti-asthma drugs (2016)
  • Author(s): Izuhara K, Suzuki S, Ogawa M, Ohta S, Nanri Y
  • Organizer: 31st Collegium Internationale Allergologicum 2016
  • Place of Presentation: Charleston (USA)
  • Year and Date: 2016-04-06
  • Int'l Joint Research
• [Book] Allergies: Current challenges and solutions (2016)
  • Author(s): Izuhara K, Matsumoto H, Nagasaki T, Ohta S, Ono J, Kinki Hokuriku Airway Disease Conference
  • Total Pages: 239
  • Publisher: Pacini Editore Medicina