Establishment of the laboratory diagnostic method to stratify the pathology and risk of developing antiphospholipid syndrome

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07318
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Yamaguchi University
• Principal Investigator: Nojima Junzo 山口大学, 大学院医学系研究科, 教授 (30448071)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 抗リン脂質抗体症候群 / 抗カルジオリピン/β2グリコプロテインⅠ抗体 / 抗ホスファチジルセリン/プロトロンビン抗体 / 動脈硬化症

Outline of Final Research Achievements

In this study, we hypothesized that anti-phospholipid antibodies advance arteriosclerosis through interactions between vascular endothelial cells, monocytes, and lymphocytes, causing arterial thromboembolism. To test this hypothesis, we created a contact co-culture model in which human aortic vascular endothelial cells seeded on Type I collagen and healthy peripheral blood mononuclear cells can interact directly through adhesion. Using the established contact co-culture model, we investigated whether antiphospholipid antibodies promote the adhesion of monocytes and various lymphocytes to vascular endothelial cells and infiltration into the collagen gel layer. As a result, we confirmed that adding APS-IgG purified from APS patient plasma to the co-culture model promoted adhesion and infiltration of monocytes and lymphocytes to vascular endothelial cells.

Free Research Field

血栓止血

Academic Significance and Societal Importance of the Research Achievements

抗リン脂質抗体症候群（APS)における動脈血栓塞栓症の発症機序を明らかにする上で，抗リン脂質抗体の作用を受けた血管内皮細胞や免疫担当細胞，さらには活性化血小板による相互作用のメカニズムの解明は重要である．本研究ではAPS患者血中に近い血管内皮細胞と単核球の共培養モデルを用いることにより，抗リン脂質抗体が免疫担当細胞の接着と血管内皮下への浸潤を促進し，動脈硬化を進展させる可能性を見出した．本研究成果は、APSにおける動脈血栓塞栓症の病態解明のみならず新規治療法の開発にも結びつく知見であり、学術的意義は大きいと考える．