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

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17728
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Akita 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
• 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

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.

Free Research Field

腎臓

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。