Analysis of autoantigen complexes on the cell surface related to the pathogenesis of autoimmune nephritis.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08622
• 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: Fujita Health University
• Principal Investigator: Miura Keiji 藤田医科大学, 保健衛生学部, 講師 (20199946)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 抗血管内皮細胞抗体 / 自己抗体 / 自己抗原 / 細胞表面抗原 / 血管炎

Outline of Final Research Achievements

The original plan was to strain lymphoblastoid cell lines from lymphocytes from patients with autoimmune nephritis using the EB virus, and to outsource the cloning of autoantibody-producing cells. However, the service was discontinued and the research methodology was changed.
Therefore, a classical immunoprecipitation method was employed. IgG was purified from several patient sera and reacted with the membrane fraction of vascular endothelial cells (HUVECs). Proteins bound to IgG were recovered and subjected to proteomic analysis. Seventy-three proteins were identified that were detected only in patient serum. Furthermore, seven proteins that are assumed to be localized to the plasma membrane were identified by Proteome discoverer analysis. We are now conducting experiments to confirm whether these proteins can be identified as new self-antigens.

Free Research Field

分子免疫学

Academic Significance and Societal Importance of the Research Achievements

多様な自己免疫疾患には、それぞれ特徴的な自己抗原が同定され、各疾患の診断基準となる検査に使われている抗原も多い。しかしそれら自己抗原の多くが細胞内に局在するタンパク質であるのに対し、患者血清中には細胞表面に結合する自己抗体、例えば抗血管内皮細胞抗体（AECA）が検出されることも多く、その矛盾は長年の疑問である。
本研究では、自己免疫性腎炎患者血清中に存在する自己抗体の中に、血管内皮細胞表面に局在する膜タンパクに結合する抗体がある、という観点から、その膜タンパクを同定し、新規自己抗原として検査や病態解明に利用することを目的とした。現在までに、７つの候補タンパクが同定され、確認実験を実施中である。