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A novel disease concept of monoclonal immunoglobulin-induced renal injury: clinicopathologic picture and pathogenesis

Research Project

Project/Area Number 19K17728
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53040:Nephrology-related
Research InstitutionAkita University

Principal Investigator

Nara Mizuho  秋田大学, 医学部附属病院, 医員 (90769944)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords単クローン性免疫グロブリン / 腎疾患 / 臨床病理像 / 構造解析 / 単クリーン性免疫グロブリン / 腎障害 / MGRS / 発症機序
Outline of Research at the Start

腎臓は単クローン性免疫グロブリンの主要な標的臓器である。最近、多発性骨髄腫の前段階で良性と捉えられてきたmonoclonal gammopathy of undetermined significanceの経過中に腎障害を呈した症例の疾患概念として、「monoclonal gammopathy of renal significance: MGRS」の呼称が提唱された。その病理像は多彩で臨床像も含めた全体像の把握が今後の重要課題である。当科には国内最多のMGRS症例の集積があり、MGRS症例の臨床病理像の詳細を明らかにしM蛋白の構造特性と病理病型との関連性を検討し高齢者医療に貢献する。

Outline of Final Research Achievements

After purification of λ-type M protein from urine of patients with crystalline columnar nephropathy and identification of the N-terminal amino acid sequence, cDNA was prepared from bone marrow blood and the full-length cDNA of this M protein was cloned. The λ-type M protein purified from urine was crystallized and analyzed by X-ray structure analysis. M-protein was purified from the urine of a myeloma patient with a large amount of κ-type M-protein in the urine but mild renal impairment, the N-terminal amino acid sequence was identified, cDNA was prepared from bone marrow blood, and the full-length cDNA of this M-protein was cloned. We also purified λ-type M protein from the urine of one patient with λ-type LCDD and found it to have a highly hydrophobic feature.

Academic Significance and Societal Importance of the Research Achievements

本研究課題と関連する腎症の臨床病理学的解析を進め、更に、種々の病型を呈した患者尿からM蛋白を精製し、構造解析に進展があった。M蛋白の構造特性と病理病型との関連性を明らかにすることは、非侵襲的な診断法の開発に繋がり、創造性の高い研究であった。高齢者医療で特に重要な血液・腎疾患分野で、診断と治療の向上に貢献をはかることは、MGRSは高齢者に多いことから、高齢者医療への波及効果も大きい。これらの稀な疾患の検討は、臨床病理学的な観点の解析からも、各疾患群の特徴や腎予後なども明らかになりつつある。

Report

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

    (2 results)

All 2020 2019

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

  • [Journal Article] Multiple Myeloma-Associated Ig Light Chain Crystalline Cast Nephropathy2020

    • Author(s)
      Matsumura, H., Furukawa, Y.,Nakagaki, T., Furutani, C., Osanai, S., Noguchi, K., Odaka, M., Yohda, M., Ohtani, H., Michishita, Y., Kawabata, Y., Kitabayashi, A., Ikeda, S., Nara, M., Komatsuda, A., Takahashi, N., Wakui, H.
    • Journal Title

      Kidney International Reports

      Volume: 5 Issue: 9 Pages: 1595-1602

    • DOI

      10.1016/j.ekir.2020.06.026

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 単クローン性免疫グロブリン惹起性腎障害の新規疾患概念2019

    • Author(s)
      奈良瑞穂
    • Organizer
      秋田県腎不全研究会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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