2018 Fiscal Year Final Research Report
Definitive molecules for pathogenesis of glomerulonephritis
| Project/Area Number |
16K08698
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Kyorin University (2017-2018)
Nippon Medical School (2016) |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 糸球体腎炎 / 質量分析 |
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| Outline of Final Research Achievements |
Some cases of glomerulonephritis pose problems in accurate typing of glomerulonephritis due to lack of approproate tool for dissecting molecules responsible for glomerular lesions. We thus utlized technique of laser microdissection (LMD) and tandem mass spectrometry-based proteomic analysis (LC-MS/MS)as a sensitive and specific tool for the diagnosis of glomerulonephriatis. Using kidney specimens, we successfully diagnose accurately the type of amyloid deposited in the glomeruli while immunofluorescence or immunohistochemistry failed to reveal amyloid precursors. Especially, our system was very useful for amyloid cases diagnosed solely at autopsy because serum or urine samples of autopsy cases were generally unavailable for further testing of precursors such as free light chains. In addition, we successfully determined non-amyloid depositions such as apoE and fibrinogen using renal biopsy specimens with LMD and LC-MS/MS.
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| Free Research Field |
人体病理学
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| Academic Significance and Societal Importance of the Research Achievements |
糸球体腎炎の診断は糸球体の光学顕微鏡を用いた形態変化に基づいてなされるが、軽微な形態変化である場合、観察者間のばらつきが大きく診断の確定が困難である症例がしばしば経験される。今回、形態以外の客観的指標を確立するため質量分析を用いた解析を行った。結果、アミロイドーシスのみならず、apoEやfibrinogenの沈着による糸球体病変を証明することができ、適切な治療法の提案、開発につなげることができた。従来の沈着症の概念が大きく変わる可能性が示唆された。
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