Identification of pathogenesis of novel autoantibodies in Takayasu arteritis

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17419
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Tohoku University
• Principal Investigator: Tomoyuki Mutoh 東北大学, 医学系研究科, 非常勤講師 (10868235)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 高安動脈炎

Outline of Final Research Achievements

A comprehensive genetic analysis using multiple PCR arrays showed marked increase in CXCL8 and marked decrease in CXCL10 following HDL addition, while marked decrease in CCL2 was observed following APC addition.
Aortic tissue samples from three surgically treated TAK patients and non-TAK patients were assessed by immunohistological staining, which showed inflammatory cell infiltration around the vasculature, a nutritive vessel in the aortic wall. In addition, EPCR and SR-BI expression was observed in endothelial cells on the luminal side of the damaged aortic vessels, with stronger expression in the vasa vasorum.

Free Research Field

Rheumatology

Academic Significance and Societal Importance of the Research Achievements

PCRアレイによる網羅的遺伝子解析の結果により、CXCL8、CXCL10、CCL2などのケモカインの関与が示唆された。これらのケモカインはMAPK(mitogen-activated protein kinase：分裂促進因子活性化タンパク質キナーゼ)シグナル伝達経路が主に関与すると考えられており。さらなる解析により、関与するパスウェイを明らかにすることで、未だ治療法が少ないTAKにおいて、新規治療標的につながる可能性が高いと考えられる。また免疫染色の結果よりvaso vasorumがTAKの炎症の首座となっている可能性も示唆され、病態解明につながったと考えられる。