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Prediction of rheumatoid arthritis onset in the pre-clinical stage

Research Project

Project/Area Number 21K08461
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54020:Connective tissue disease and allergy-related
Research InstitutionNagasaki University

Principal Investigator

Tamai Mami  長崎大学, 医歯薬学総合研究科(医学系), 准教授 (60380862)

Co-Investigator(Kenkyū-buntansha) 植木 優夫  長崎大学, 総合生産科学研究科(情報データ科学系), 教授 (10515860)
川尻 真也  長崎大学, 医歯薬学総合研究科(医学系), 准教授 (20457576)
柳原 克紀  長崎大学, 医歯薬学総合研究科(医学系), 教授 (40315239)
大山 要  長崎大学, 病院(医学系), 教授 (50437860)
川上 純  長崎大学, 医歯薬学総合研究科(医学系), 教授 (90325639)
鵜飼 孝  長崎大学, 病院(歯学系), 教授 (20295091)
Project Period (FY) 2021-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2024: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords関節リウマチ / 早期関節炎 / 発症予測 / 人工知能
Outline of Research at the Start

関節リウマチ発症リスクの解明が進むにつれて発症抑制の対象が未分類早期関節炎から、臨床的関節炎をきたしていないが関節痛がある者、MRIあるいは関節超音波で検出される炎症を有する自己抗体陽性者へシフトしている。本研究はMRI、関節超音波を用いて臨床的関節炎を呈していないRA発症高リスク者をスクリーニングし、発症に至る過程でRA特異的自己抗体である抗シトルリン化蛋白抗体の性状変化や質量分析を用いたRA特異的新規自己抗体発現の変化、口腔マイクロバイオームの変化を前向きにフォローアップし、遺伝素因を含めて得られたデータを人工知能で解析しRA発症の予測モデルを確立する。

Outline of Final Research Achievements

This study aimed to establish a predictive model for the onset of rheumatoid arthritis (RA) by taking a multifaceted approach to target the preclinical stage of the disease. Of the 68 patients who visited an early arthritis clinic, five presented with joint pain without clinical arthritis (CSA), and 14 were classified as having unclassified early arthritis (UA). Of these, 25% of CSA cases and 50% of UA cases progressed to RA within two and one months, respectively. Oral microbiota analysis revealed differences in bacterial communities between the RA group and the control group. While the study did not achieve the required number of cases for establishing a predictive model, valuable insights were gained.

Academic Significance and Societal Importance of the Research Achievements

多角的アプローチから早期にRA発症を予測するモデルを人工知能を用いて解析するという先端的な研究であったが、症例数が少なく解析に至らなかった。しかしながら口腔内細菌叢に着目したRA発症に関する研究は少なく、本研究では少ない症例ながらもRAと非RAにおける口腔内細菌叢が異なることを明らかにした。また社会的には口腔内細菌叢がRA発症に及ぼす影響を喚起する意味で重要である。

Report

(5 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (20 results)

All 2025 2024 2023 2022 2021

All Journal Article (9 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (11 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] IgM antibodies against acetylated proteins as a possible starting point of the anti-modified protein antibody response in rheumatoid arthritis.2024

    • Author(s)
      van Wesemeal TJ, Reijm S, Kawakami A, Dorjee A, Stoeken G, Maeda T, Kawashiri SY, Huizinga TWJ, Tamai M, Toes REM, van der Woude D.
    • Journal Title

      Annals of Rheumatic Diseases

      Volume: 83 Issue: 2 Pages: 267-270

    • DOI

      10.1136/ard-2023-224553

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Predictive Value of Magnetic Resonance Imaging-detected Tenosynovitis of the Metacarpophalangeal and Wrist Joints for the Development of Rheumatoid Arthritis among Patients with Undifferentiated Arthritis2023

    • Author(s)
      Tamai M, Grundeken V, Arima M, Brinck RT, van der Helm-van Mil AHM, Ohki N, Uetani M, Kawakami A.
    • Journal Title

      Internal Medicine

      Volume: 62 Issue: 16 Pages: 2329-2334

    • DOI

      10.2169/internalmedicine.0077-22

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2023-08-15
    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] ACPA‐IgG variable domain glycosylation increases before the onset of rheumatoid arthritis and stabilizes thereafter; a cross‐sectional study encompassing 1500 samples2022

    • Author(s)
      Kissel T, Hafkenscheid L, Wesemael TJ, Tamai M, Kawashiri SY, Kawakami A, El-Gabalawy HS, van Schaardenburg D, Rantapaa-Dahlqvist S, Wuhrer M, van der Helm-van Mi AHM, Allaart CF, van der Woude D, Scherer HU, Toes REM, Huizinga TWJ.
    • Journal Title

      Arthritis & Rheumatology

      Volume: - Issue: 7 Pages: 1147-1158

    • DOI

      10.1002/art.42098

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cross-reactivity of anti-modified protein antibodies is also present in predisease and individuals without rheumatoid arthritis2022

    • Author(s)
      Reijm Sanne、Brehler Astrid S、Rantapaa-Dahlqvist Solbritt、Kawakami Atsushi、Maeda Takahiro、Kawashiri Shin-ya、Tamai Mami、van der Woude Diane、Toes Rene EM
    • Journal Title

      Annals of the Rheumatic Diseases

      Volume: 81 Issue: 9 Pages: 1332-1334

    • DOI

      10.1136/annrheumdis-2022-222326

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Prediction of radiographic progression during a treat-to-target strategy by the sequential application of MRI-proven bone marrow oedema and power-Doppler grade ≧2 articular synovitis in rheumatoid arthritis: Retrospective observational study2022

    • Author(s)
      Takatani Ayuko、Tamai Mami、Ohki Nozomi、Okamoto Momoko、Endo Yushiro、Tsuji Sousuke、Shimizu Toshimasa、Umeda Masataka、Fukui Shoichi、Sumiyoshi Remi、Nishino Ayako、Koga Tomohiro、Kawashiri Shin-ya、Iwamoto Naoki et al.
    • Journal Title

      Modern Rheumatology

      Volume: - Issue: 4 Pages: 708-714

    • DOI

      10.1093/mr/roac077

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] RA発症前の病態解析の進歩:環境要因からの解析2022

    • Author(s)
      辻 良香、玉井慎美、川上 純
    • Journal Title

      臨床リウマチ

      Volume: 34

    • Related Report
      2021 Research-status Report
  • [Journal Article] Evolution of anti-modified protein antibody responses can be driven by consecutive exposure to different post-translational modifications2021

    • Author(s)
      Volkov M, Kampstra ASB. Van Schie KA, Kawakami A. Tamai M, Kawashiri SY, T Maeda T, Huizinga TWJ, Toes REM , Van der Woude D.
    • Journal Title

      Arthritis Research & Therapy

      Volume: 23 Issue: 1 Pages: 298-298

    • DOI

      10.1186/s13075-021-02687-5

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genetic predisposition (HLA-SE) is associated with ACPA-IgG variable domain glycosylation in the predisease phase of RA2021

    • Author(s)
      Kissel T, Wesemael TJV, Lundquist A, Kokkonen H, Kawakami A, Tamai M, Schaardenburg DV, Wuhrer M, Huizinga TWJ, Scherer HU, Woude DVD, Dahlqvist SR, Toes REM.
    • Journal Title

      Annals of the Rheumatic Diseases

      Volume: 81 Issue: 1 Pages: 141-143

    • DOI

      10.1136/annrheumdis-2021-220841

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 画像診断の最新知見2021

    • Author(s)
      辻 良香、玉井慎美、川尻真也、川上 純
    • Journal Title

      日本臨床

      Volume: 79 Pages: 1302-1308

    • Related Report
      2021 Research-status Report
  • [Presentation] 地域における関節リウマチ発症追跡研究:Nagasaki Island Study2025

    • Author(s)
      玉井慎美,野中文陽,辻 良香,川尻真也 、有馬和彦,青柳 潔,前田隆浩、川上 純
    • Organizer
      日本疫学会総会
    • Related Report
      2024 Annual Research Report
  • [Presentation] Prospective study of the development of rheumatoid arthritis in residents’ health check-ups; Nagasaki Island Study2025

    • Author(s)
      Mami Tamai, Yoshika Tsuji, Fumiaki Nonaka, Shin-ya Kasashiri, Kazuhiko Arima, Kiyoshi Aoyagi, Takahiro Maeda, Atsushi Kawakami
    • Organizer
      6TH JAPAN-G(ERMANY SYMPOSIUM ON ADVANCED PREVENTIVE MEDICINE
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 健常人における高リスク群からの関節リウマチ発症予測:Nagasaki Island Study2024

    • Author(s)
      玉井慎美,野中文陽,辻 良香,川尻真也 、古藤世梨奈、有馬和彦,青柳 潔,前田隆浩、川上 純
    • Organizer
      日本リウマチ学会総会
    • Related Report
      2024 Annual Research Report
  • [Presentation] 健常人における関節リウマチ発症高リスク群からの発症予測:Nagasaki Island Study2023

    • Author(s)
      玉井慎美, 野中文陽 辻良香, 川尻真也, 古藤世梨奈, 有馬和彦, 青柳潔, 前田隆浩, 川上純
    • Organizer
      日本リウマチ学会総会
    • Related Report
      2023 Research-status Report
  • [Presentation] 関節リウマチの発症予測の試み:Nagasaki Ialnad Study (NaIS)2022

    • Author(s)
      玉井慎美、野中文陽、川尻真也、有馬和彦、青柳 潔、川上 純
    • Organizer
      第66回日本リウマチ学会総会・学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] Investigation of oral microbiome in rheumatoid arthritis regarding to ACPA and HLA DRB1*SE: Nagasaki Island Study2022

    • Author(s)
      Yoshika Tsuji, Mami Tamai, Fumiaki Nonaka, Shin-ya Kawashiri, Kazuhiko Arima, Atsushi Kawakami
    • Organizer
      第66回日本リウマチ学会総会・学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 関節リウマチにおける画像所見と治療経過に歯周疾患が及ぼす影響の検討2022

    • Author(s)
      玉井慎美、高谷亜由子、住吉伶美、川尻真也、川下由美子、大木 望、上谷雅孝、川上 純
    • Organizer
      第50回日本臨床免疫学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 欧州リウマチ学会スコアによる関節リウマチ発症の予測:Nagasaki Island Study(NaIS)2022

    • Author(s)
      玉井慎美,野中文陽,川尻真也,有馬和彦, 青柳 潔,前田隆浩,川上 純
    • Organizer
      第32回日本疫学会学術総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 住民健康診査におけるリウマチ二次検診の前向き研究2021

    • Author(s)
      玉井慎美, 永吉真子, 野中文陽, 川尻真也, 有馬和彦, 青柳潔, 川上純
    • Organizer
      第65回日本リウマチ学会総会・学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Clinical suspicious arthralgiaスコアと自己抗体による関節リウマチ発症予測2021

    • Author(s)
      玉井慎美,野中文陽,川尻真也,有馬和彦,川上 純
    • Organizer
      第36回日本臨床リウマチ学会
    • Related Report
      2021 Research-status Report
  • [Presentation] The Workshop of Imaging: MRI: Wrap-up Session: MRI in Rheumatology2021

    • Author(s)
      Mami Tamai
    • Organizer
      APLAR 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2026-01-16  

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