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Pathogenetic role of ectopic lymphoid organs formed in IgG4-related vascular lesions

Research Project

Project/Area Number 20K08504
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionDepartment of Clinical Research, National Hospital Organization Kanazawa Medical Center

Principal Investigator

Kasashima Fuminori  独立行政法人国立病院機構(金沢医療センター臨床研究部), その他部局等, その他 (90303304)

Co-Investigator(Kenkyū-buntansha) 川島 篤弘  独立行政法人国立病院機構(金沢医療センター臨床研究部), その他部局等, その他 (20242563)
松本 康  独立行政法人国立病院機構(金沢医療センター臨床研究部), その他部局等, その他 (20262579)
笠島 里美  金沢大学, 保健学系, 教授 (20444200)
尾崎 聡  金沢大学, 保健学系, 助教 (40401921)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsIgG4-related disease / IgG4-AAA / follicular helper T cell / reguratory T cell / Tertiary lymphoid organs / IgG4関連血管病変 / 濾胞性T細胞 / 3次性リンパ組織 / IgG4関連疾患 / 大血管炎 / 異所性リンパ組織 / 三次性リンパ組織
Outline of Research at the Start

IgG4-VDは新しい疾患概念であるため,その病因,病態については未だ不明な点が多い.近年,濾胞性T細胞は,濾胞内でB細胞の形質芽細胞への分化誘導を行い,各種自己免疫性疾患に関連する事が報告されている.動脈外膜に形成される異所性リンパ組織(ATLOs)がIgG4-VDに存在する事はこれまで報告されてきたが,その意義は不明であった.本研究では,IgG4-VDにおけるATLOsの数,分布や形状,ATLOs内の免疫細胞の分布や発現形式を解析する事により,ATLOsとIgG4-VDの病因,病態並びに病期の関連性を解明する.

Outline of Final Research Achievements

IgG4-AAA (typical IgG4-related vascular disease) was characterized by numerous, large, irregular-shaped arterial tertiary lymphoid organs(ATLOs), and higher numbers of Tfr and Tfh2 cells than Tfh1 cells were present compared to patients with other vascular diseases. The morphological abnormalities (in number, area, and form) of ATLOs in IgG4-AAA and the increased number of Tfr cells are closely related to the activity of IgG4-related disease, including the number of IgG4-positive plasmacytes and the degree of adventitial thickness. An increase in Tfr cells in IgG4-AAA was associated with ATLO formation. Increased Tfh17 cells were found in TKA, and aAAA and non-IgG4-IAAA were characterized by increased Tfh1 cells.IgG4-AAA should be positioned as adventitial vasculitis with predominant Tfr and Tfh2 cells, accompanied by the abnormal appearance of ATLOs.

Academic Significance and Societal Importance of the Research Achievements

IgG4関連血管病変(IgG4-VD)は,血清IgG4高値や動脈外膜を中心としたIgG4陽性細胞浸潤を特徴とする炎症性動脈病変の新しい疾患概念である.IgG4-VDでは組織学的診断が困難な例があり,より確実な診断指標が求められている.本研究では,IgG4-VDにおけるTfr, Tfh2優位のT細胞サブセットは異常ATLOs形成およびIgG4-RDの活動性に関連する事が示唆された.IgG4-VDに特徴的なT細胞サブセットおよび形態学的に不整なATLOsは今後の組織診断においても有用である.

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (7 results)

All 2023 2022 2021

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (4 results)

  • [Journal Article] Ultrasonic Wave Pericardiectomy for IgG4-related Constrictive Pericarditis2022

    • Author(s)
      Matsumoto Yasushi、Kasashima Satomi、Kasashima Fuminori
    • Journal Title

      The Annals of Thoracic Surgery

      Volume: - Issue: 5 Pages: e327-e329

    • DOI

      10.1016/j.athoracsur.2021.12.065

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] The disturbance of the distribution of T helper cell subsets in the mantle area surrounding germinal centers in immunoglobulin G4?related sclerosing sialadenitis2022

    • Author(s)
      Kasashima Satomi、Kawashima Atsuhiro、Kurose Nozomu、Ozaki Satoru、Ikeda Hiroko、Harada Kenichi
    • Journal Title

      Virchows Archiv

      Volume: 481 Issue: 5 Pages: 767-777

    • DOI

      10.1007/s00428-022-03384-7

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regional disturbance of the distribution of T regulatory cells and T helper cells associated with irregular-shaped germinal centers in immunoglobulin G4-related sialadenitis2021

    • Author(s)
      Kasashima Satomi、Kawashima Atsuhiro、Kurose Nozomu、Ozaki Satoru、Ikeda Hiroko、Harada Ken-Ichi
    • Journal Title

      Virchows Archiv

      Volume: 479 Issue: 6 Pages: 1221-1232

    • DOI

      10.1007/s00428-021-03187-2

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] IgG4関連硬化唾液腺における 3次リンパ組織形成異常 及び helper T細胞サブセット不均衡2023

    • Author(s)
      笠島里美,川島篤弘,黒瀬望,尾崎聡.原田憲一
    • Organizer
      第14回日本IgG4関連疾患学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 巨細胞性動脈炎・高安動脈炎・IgG4関連疾患におけるヘルパーT細胞サブセットの検討2023

    • Author(s)
      五十嵐まど佳,笠島里美,尾崎聡,小嶋洋美,梅原瑤子,黒瀬望,川島篤弘
    • Organizer
      第61回日本臨床検査医学会東海北陸支部総会/第346回日本臨床化学会 東海北陸支部例会連合大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] IgG4関連血管病変の血管濾胞内のT細胞亜分画の解明2023

    • Author(s)
      笠島里美,川島篤弘,黒瀬望,尾崎聡
    • Organizer
      第112回日本病理学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] IgG4関連硬化性唾液腺炎における胚中心周辺のマントル領域におけるTヘルパー細胞サブセットの特異的な異常分布2022

    • Author(s)
      笠島里美,川島篤弘,黒瀬望,尾崎聡.原田憲一,池田博子
    • Organizer
      第111回日本病理学会総会
    • Related Report
      2022 Annual Research Report

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Published: 2020-04-28   Modified: 2024-12-25  

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