2022 Fiscal Year Final Research Report

The identification of the antigen and deposition proteins in glomerulonephritis and glomerular deposition diseases

Research Project

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Project/Area Number	20K08619
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 53040:Nephrology-related
Research Institution	Nippon Medical School
Principal Investigator	Shimizu Akira 日本医科大学, 大学院医学研究科, 大学院教授 (00256942)
Co-Investigator(Kenkyū-buntansha)	石井永一日本医科大学, 大学院医学研究科, 研究生 (00193243) 桑原尚美日本医科大学, 医学部, テクニカルスタッフ (00599011)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	質量分析 / LC-MS/MS法 / プロテオミクス / 腎生検 / レーザーマイクロダイセクション / 糸球体沈着症 / 免疫複合体型糸球体腎炎 / 腎病理診断
Outline of Final Research Achievements	To identify the antigens in several immune complex type glomerulonephritis and to analyze deposited proteins in several glomerular deposition diseases, we performed laser microdissection-liquid chromatography tandem mass spectrometry (LC-MS/MS)-based proteomic analysis using formalin-fixed paraffin embedded renal biopsy kidney tissues. We progressed to identify several antigens in primary and secondary membranous nephropathy and immune complex type glomerulonephritis. We also analyzed several deposited proteins in glomerular diseases to identify DNAJB9 in Fibrillary GN, fibrinogen in Cryofibrinogen glomerulopathy, monoclonal immunoglobulin in monoclonal immunoglobulin deposition diseases, and complement activated proteins demonstrated activation of the complement pathway, and these cases were reported as case report in several journals.
Free Research Field	病理学 (腎臓病理学)
Academic Significance and Societal Importance of the Research Achievements	本研究は、腎生検病理検体から、液体グロマトグラフィ/タンデム質量分析法(LC-MS/MS法)を用いた微量蛋白質解析を行い、免疫複合体型糸球体疾患の既存の抗原蛋白質の同定が可能であることを確認した。また、糸球体沈着症に関連した蛋白質の同定を行い、疾患関連蛋白質が明らかな疾患の腎生検検体からの解析を進め、確定診断に至った症例を報告した。腎生検病理検体を用いたLC-MS/MS法の解析は、腎疾患の発症・進展機序の解析や確定診断に貢献することを示し、疾患関連蛋白質の解析の継続する意義を明らかにした。