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The role of glycosylation of the serum IgG in rheumatoid arthritis

Research Project

Project/Area Number 18K08399
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 InstitutionNational Hospital Organization Osaka-Minami Medical Center

Principal Investigator

Shiro Ohshima  独立行政法人国立病院機構(大阪南医療センター臨床研究部), その他部局等, 部長 (50362728)

Co-Investigator(Kenkyū-buntansha) 和田 芳直  地方独立行政法人大阪府立病院機構大阪母子医療センター(研究所), その他部局等, 母性内科・医師 (00250340)
大海 雄介  中部大学, 生命健康科学部, 助教 (10584758)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords関節リウマチ / 免疫グロブリン / 糖鎖異常 / 糖鎖 / シアル酸
Outline of Final Research Achievements

We analyzed the sugar chain structure of IgG in RA using the novel technique, and examined its value as a marker for early diagnosis. IgG was extracted from the serum of RA patients, and the proportion of galactose-deficient IgG (G0) and sialic acid-deficient IgG (S0) was analyzed by a sugar chain analysis method combining high performance liquid chromatography (HPLC) and mass analysis (MS). Furthermore, the addition rate of sialic acid was examined using MS. The proportions of G0 and S0 were significantly higher in RA than in healthy subjects. Furthermore, MS revealed that the rate of S0 was high in RA. These abnormalities were observed from the early stage of onset, and it was also confirmed that they decreased in remission. Glycosylation abnormalities may be useful as markers for RA diagnosis, activity, and remission. Furthermore, it was suggested that these abnormalities might play a important role in the etiology and pathophysiology.

Academic Significance and Societal Importance of the Research Achievements

RAは病因が明らかでないため、長期間の治療継続を余儀なくされることは、医学的問題のみならず、医療費においても大きな社会的問題となっている。
分子標的治療の登場により、臨床的寛解が現実的な目標となり更にその先に薬剤を中止してなお維持するいわゆるbio free寛解も目指せるようになった。今回、免疫グロブリンの糖鎖異常の測定が免疫学的寛解のマーカーとして有用性が明らかになったことで、投与薬剤の中止や減量の指標となり、医療費の削減にも繋がる可能性があると考えられる。さらに糖鎖異常のメカニズムが明らかになれば、RAの診断、予後評価に繋がるマーカーの開発や根本的な治療につながるものと考えられる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (4 results)

All 2021 2020 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results)

  • [Journal Article] An infectivity-enhancing site on the SARS-CoV-2 spike protein targeted by antibodies2021

    • Author(s)
      Liu Y, Ohshima S, Arase H, et al.
    • Journal Title

      Cell

      Volume: Jun 24;184(13) Issue: 13 Pages: 3452-3466

    • DOI

      10.1016/j.cell.2021.05.032

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 関節リウマチにおけるIgG糖鎖異常の解析2021

    • Author(s)
      大島至郎
    • Organizer
      日本リウマチ学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 関節リウマチにおけるIgG糖鎖異常の解析2020

    • Author(s)
      大島至郎
    • Organizer
      日本リウマチ学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 高齢関節リウマチに対するトシリズマブの長期治療例の検討2019

    • Author(s)
      大島至郎
    • Organizer
      日本リウマチ学会
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2024-01-30  

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