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Generation of evidence through registry construction by genome-wide subtype analysis of Behcet's disease

Research Project

Project/Area Number 19H03700
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 54020:Connective tissue disease and allergy-related
Research InstitutionYokohama City University

Principal Investigator

KIRINO Yohei  横浜市立大学, 医学部, 講師 (50468154)

Co-Investigator(Kenkyū-buntansha) 小林 大介  新潟大学, 医歯学総合病院, 助教 (00363507)
渥美 達也  北海道大学, 大学病院, 教授 (20301905)
吉藤 元  京都大学, 医学研究科, 講師 (20422975)
國崎 玲子  横浜市立大学, 附属市民総合医療センター, 准教授 (20457849)
中島 秀明  横浜市立大学, 医学研究科, 教授 (30217723)
田中 良哉  産業医科大学, 医学部, 教授 (30248562)
岳野 光洋  日本医科大学, 医学部, 准教授 (50236494)
土橋 浩章  香川大学, 医学部, 准教授 (50380176)
目黒 明  横浜市立大学, 医学研究科, 特任教授 (60508802)
寺尾 知可史  国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (60610459)
黒沢 美智子  順天堂大学, 医学部, 准教授 (70245702)
東野 俊洋  北里大学, 医学部, 講師 (70458818)
吉見 竜介  横浜市立大学, 医学部, 講師 (70585265)
藤枝 雄一郎  北海道大学, 大学病院, 助教 (70790872)
菊地 弘敏  帝京大学, 医学部, 准教授 (80338681)
竹内 正樹  横浜市立大学, 医学研究科, 特任准教授 (80794081)
廣畑 俊成  帝京大学, 医学部, 客員教授 (90189895)
川上 純  長崎大学, 医歯薬学総合研究科(医学系), 教授 (90325639)
水木 信久  横浜市立大学, 医学研究科, 教授 (90336579)
古賀 智裕  長崎大学, 医歯薬学総合研究科(医学系), 助教 (90537284)
宮川 一平  産業医科大学, 大学病院, 助教 (10525463)
大村 浩一郎  京都大学, 医学研究科, 特命准教授 (40432372)
Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2023: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2022: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2020: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywordsベーチェット病 / レジストリ研究 / 疾患活動性 / 予後不良病型 / レジストリ / ゲノム解析 / クラスター解析 / GWAS / 疾患活動性指標 / 難病プラットフォーム / 疾患レジストリ / 遺伝学的解析 / 亜型解析 / サイトカイン
Outline of Research at the Start

完全型ベーチェット病と腸管型ベーチェット病が異なる疾患集団であることを、遺伝学・疫学・免疫学の統合的解析により証明し、診断基準の改訂や個別化医療の開発に資するエビデンスを構築する。本多施設共同研究によってBDの疾患レジストリを構築してさらに症例数を増加させて検出力を上げることは世界的にみても独自性が高い研究といえる。個々の亜型と関連する疾患感受性遺伝子が判明すれば、病態の相違、類似性の手がかりになり、将来的には診断基準の改訂、予後予測因子の同定、亜型毎の診療ガイドライン作成、病態に応じた治療につながるものと期待される。

Outline of Final Research Achievements

Treat-to-target strategies have not been developed for Behcet's disease (BD), which may be disadvantageous to patients. In addition, little is known about the relationship between disease activity and the incidence of inflammatory major organ events in BD. In this Behcet's disease registry study, we prospectively examined the association between BDCAF, a measure of disease activity in Behcet's disease, and the incidence of inflammatory major organ events (defined as inflammation of the eye, central nervous system, bowel, and vascular system in BD) for 3 years. Results showed that the incidence of inflammatory major organ events was significantly higher in patients with residual overall disease activity. In addition, higher serum IL-6 levels were associated with higher incidence of inflammatory major organ events. These results suggest that targeted treatment strategies and monitoring of serum IL-6 may be useful in preventing the development of inflammatory major organ events in BD.

Academic Significance and Societal Importance of the Research Achievements

本研究成果から、ベーチェット病において全体的な疾患活動性指標BDCAFを低くすることを標的とした治療戦略と、血清IL-6のモニタリングが、BDにおける炎症性主要臓器イベントの予防に役立つ可能性が世界で始めて証明された。この研究成果を受けて、ベーチェット病全国レジストリ研究へと研究を飛躍させることができた。また、本研究成果を検証しつつ、将来的なベーチェット病診療ガイドラインの改訂を目指す方向性を確立する動機付けとなった。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (36 results)

All 2024 2023 2022 2021 2020 2019

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 5 results) Presentation (21 results) (of which Int'l Joint Research: 16 results,  Invited: 15 results) Book (5 results)

  • [Journal Article] Association of high disease activity and serum IL-6 levels with the incidence of inflammatory major organ events in Behcet disease: a prospective registry study2024

    • Author(s)
      Hirahara Lisa、Kirino Yohei、Soejima Yutaro、Iizuka Yuki、Yoshimi Ryusuke、Fujieda Yuichiro、Atsumi Tatsuya、Tono Toshihiro、Kobayashi Daisuke、Meguro Akira、Takeuchi Masaki、Sakamaki Kentaro、Takeno Mitsuhiro、Mizuki Nobuhisa、Nakajima Hideaki
    • Journal Title

      Frontiers in Immunology

      Volume: 15

    • DOI

      10.3389/fimmu.2024.1354969

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Replication Study of the Association of GAS6 and PROS1 polymorphisms with Behcet’s Disease in a Japanese Population2023

    • Author(s)
      Teshigawara Takeshi、Meguro Akira、Takeuchi Masaki、Ishido Mizuho、Soejima Yutaro、Hirahara Lisa、Kirino Yohei、Ohno Shigeaki、Mizuki Nobuhisa
    • Journal Title

      Ocular Immunology and Inflammation

      Volume: 32 Issue: 4 Pages: 447-453

    • DOI

      10.1080/09273948.2023.2173239

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recommendations for the management of the vascular involvement in Behçet’s disease by the Japanese National Research Committee for Behçet’s disease—secondary publication2023

    • Author(s)
      Nagafuchi Hiroko、Kikuchi Hirotoshi、Ishibash Hiroyuki、Maeda Hideaki、Ogino Hitoshi、Kirino Yohei、Sawada Tetsuji、Saito Kazuyoshi、Kuwana Masataka、Hirohata Shunsei、Ishigatsubo Yoshiaki、Niimi Masanori、Okita Yutaka、Miyata Tetsuro、Shigematsu Hiroshi、Takeno Mitsuhiro
    • Journal Title

      Modern Rheumatology

      Volume: 34 Issue: 1 Pages: 182

    • DOI

      10.1093/mr/road002

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Roles of Monocytes and Macrophages in Beh?et’s Disease With Focus on M1 and M2 Polarization2022

    • Author(s)
      Hirahara Lisa、Takase-Minegishi Kaoru、Kirino Yohei、Iizuka-Iribe Yuki、Soejima Yutaro、Yoshimi Ryusuke、Nakajima Hideaki
    • Journal Title

      Frontiers in Immunology

      Volume: 13 Pages: 852297-852297

    • DOI

      10.3389/fimmu.2022.852297

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Behcet's disease with a somatic UBA1 variant: Expanding spectrum of autoinflammatory phenotypes of VEXAS syndrome2022

    • Author(s)
      Matsumoto H、Asano T、Tsuchida N、Maeda A、Yoshida S、Yokose K、Fujita Y、Temmoku J、Matsuoka N、Yashiro-Furuya M、Sato S、Irie K、Norikawa N、Yamamoto T、Endo M、Fukuchi K、Ohkawara H、Ikezoe T、Uchiyama Y、Kirino Y、Matsumoto N、Watanabe H、Migita K
    • Journal Title

      Clinical Immunology

      Volume: 238 Pages: 108996-108996

    • DOI

      10.1016/j.clim.2022.108996

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Beneficial effects of apremilast on genital ulcers, skin lesions, and arthritis in patients with Beh?et’s disease: A systematic review and meta-analysis2021

    • Author(s)
      Iizuka Yuki、Takase-Minegishi Kaoru、Hirahara Lisa、Kirino Yohei、Soejima Yutaro、Namkoong H o、Horita Nobuyuki、Yoshimi Ryusuke、Takeuchi Masaki、Takeno Mitsuhiro、Mizuki Nobuhisa、Nakajima Hideaki
    • Journal Title

      Modern Rheumatology

      Volume: - Issue: 6 Pages: 1153-1162

    • DOI

      10.1093/mr/roab098

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Changes in the proportion of clinical clusters contribute to the phenotypic evolution of Behcet's disease in Japan.2021

    • Author(s)
      Soejima Y, Kirino Y, Mitsuhiro Takeno M, Kurosawa M, Masaki Takeuchi M, Ryusuke Yoshimi R, Sugiyama Y, Ohno S, Yukiko Asami Y, Akiko Sekiguchi A, Igarashi T, Nagaoka S, Yoshiaki Ishigatsubo Y, Hideaki Nakajima H, Mizuki N.
    • Journal Title

      Arthritis Res Ther.

      Volume: 23(1) Issue: 1 Pages: 49-49

    • DOI

      10.1186/s13075-020-02406-6

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy and safety of apremilast for 3 months in Behcet’s disease: A prospective observational study2020

    • Author(s)
      Hirahara Lisa、Kirino Yohei、Soejima Yutaro、Takeno Mitsuhiro、Takase-Minegishi Kaoru、Yoshimi Ryusuke、Takeuchi Masaki、Mizuki Nobuhisa、Nakajima Hideaki
    • Journal Title

      Modern Rheumatology

      Volume: e-pub Issue: 4 Pages: 1-6

    • DOI

      10.1080/14397595.2020.1830504

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and Genetic Aspects of Behçet's Disease in Japan2019

    • Author(s)
      Kirino Yohei、Nakajima Hideaki
    • Journal Title

      Internal Medicine

      Volume: 58 Issue: 9 Pages: 1199-1207

    • DOI

      10.2169/internalmedicine.2035-18

    • NAID

      130007641499

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2019-05-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Haploinsufficiency of A20 caused by a novel nonsense variant or entire deletion of TNFAIP3 is clinically distinct from Beh?et’s disease2019

    • Author(s)
      Tsuchida Naomi、Kirino Yohei、Soejima Yutaro、Onodera Masafumi、Arai Katsuhiro、Tamura Eiichiro、Ishikawa Takashi、Kawai Toshinao、Uchiyama Toru、Nomura Shigeru、Kobayashi Daisuke、Taguri Masataka、Mitsuhashi Satomi、Mizuguchi Takeshi、Takata Atsushi、Miyake Noriko、Nakajima Hideaki、Miyatake Satoko、Matsumoto Naomichi
    • Journal Title

      Arthritis Research & Therapy

      Volume: 21 Issue: 1 Pages: 137-137

    • DOI

      10.1186/s13075-019-1928-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 皮膚科との連携が診断に有用であった一例2023

    • Author(s)
      桐野洋平
    • Organizer
      第6回日本ベーチェット病学会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Seeking precision medicine based on the pathophysiology of Behcet's disease2023

    • Author(s)
      桐野洋平
    • Organizer
      ICCLE meeting
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 横浜市立大学ベーチェットレジストリから判明した疾患活動性の現状2023

    • Author(s)
      桐野洋平
    • Organizer
      第67回日本リウマチ学会総会
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Difficult-to-treat intestinal Behcet's disease2023

    • Author(s)
      桐野洋平
    • Organizer
      International Conference on Behcet's disease
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 難病レジストリ研究の進捗状況 ベーチェット病2022

    • Author(s)
      桐野洋平
    • Organizer
      第66回日本リウマチ学会総会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ベーチェット病疾患レジストリから判明した疾患活動性の現状2022

    • Author(s)
      平原、桐野ら
    • Organizer
      第66回日本リウマチ学会総会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] レジストリ研究から明らかとなったベーチェット病患者の病状認識と医師評価間の乖離2022

    • Author(s)
      桐野ら
    • Organizer
      第66回日本リウマチ学会総会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ベーチェット病レジストリ研究2022

    • Author(s)
      桐野洋平
    • Organizer
      第121回日本皮膚科学会総会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Difficult-to-treat intestinal Behcet's disease2022

    • Author(s)
      Yohei Kirino
    • Organizer
      International Conference on Behcet's disease
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 難病レジストリ研究の進捗状況2022

    • Author(s)
      桐野洋平
    • Organizer
      第66回 日本リウマチ学会総会
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] レジストリ研究から明らかとなったベーチェット病患者の病状認識と医師評価間の乖離2022

    • Author(s)
      桐野洋平
    • Organizer
      第66回 日本リウマチ学会総会
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ベーチェット病の難治性口腔潰瘍に対するアプレミラストの実臨床における1年間の治療成績2022

    • Author(s)
      中山裕太、桐野洋平
    • Organizer
      第66回 日本リウマチ学会総会
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 機械学習を用いたBehcet病患者の免疫学的サブセットの検討2022

    • Author(s)
      平原理紗、桐野洋平ら
    • Organizer
      第66回 日本リウマチ学会総会
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ベーチェット病患者のreal-worldにおける新型コロナウイルスワクチンの有効性・安全性2022

    • Author(s)
      副島裕太郎、桐野洋平
    • Organizer
      第66回 日本リウマチ学会総会
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A case of covid-19 Behcet's disease in Japan2020

    • Author(s)
      桐野洋平
    • Organizer
      International Society for Behet's Disease Webinar
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Molecular Genetics of Behcet’s disease and Real-world data of apremilast2020

    • Author(s)
      桐野洋平
    • Organizer
      日本研究皮膚科学会第45回年次学術大会・総会
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] リウマチ性疾患の最適化医療の開発2020

    • Author(s)
      桐野洋平
    • Organizer
      第48回 日本臨床免疫学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ベーチェット病の 難治性病態と治療2020

    • Author(s)
      桐野洋平
    • Organizer
      第64回日本リウマチ学会総会・学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ベーチェット病患者における疾患活動性残存と医師の過小評価の現状2020

    • Author(s)
      平原理紗、桐野洋平
    • Organizer
      第64回日本リウマチ学会総会・学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Nation-wide Behcet’s disease registry to identify a population of patients associated with poor prognosis. 20th2019

    • Author(s)
      Kirino Y
    • Organizer
      Annual Meeting of the Korean Society for Behcet’s Disease, Seoul, Korea
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ベーチェット病のunmet needsと治療.2019

    • Author(s)
      桐野洋平
    • Organizer
      日本臨床リウマチ学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Book] 現場がエキスパートに聞きたいベーチェット病2023

    • Author(s)
      桐野洋平
    • Total Pages
      180
    • Publisher
      日本医事新報社
    • ISBN
      9784784913978
    • Related Report
      2022 Annual Research Report
  • [Book] 私の治療 第4版 ベーチェット病2022

    • Author(s)
      桐野洋平
    • Total Pages
      1
    • Publisher
      日本医事新報社
    • Related Report
      2022 Annual Research Report
  • [Book] リウマチ科2021

    • Author(s)
      副島裕太郎、桐野洋平
    • Publisher
      科学評論社
    • Related Report
      2021 Annual Research Report
  • [Book] 医学のあゆみ2021

    • Author(s)
      桐野洋平
    • Publisher
      医歯薬出版
    • Related Report
      2021 Annual Research Report
  • [Book] 日本臨牀2021

    • Author(s)
      副島裕太郎, 桐野洋平
    • Publisher
      日本臨牀社
    • Related Report
      2021 Annual Research Report

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Published: 2019-04-18   Modified: 2025-01-30  

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