Novel syndrome based on the common pathophysiology among Takayasu arteritis and ulcerative colitis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08469
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Tohoku University
• Principal Investigator: Shirai Tsuyoshi 東北大学, 大学病院, 講師 (20646997)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 高安動脈炎 / 潰瘍性大腸炎 / プロテインC受容体 / 自己抗体 / 病態形成

Outline of Final Research Achievements

Takayasu arteritis (TAK) is a large-vessel vasculitis that affects young females. We identified two autoantibodies in TAK using SARF. The autoantigens were endothelial protein C receptor (EPCR) and scavenger receptor class B type 1 (SR-BI). Autoantibodies against EPCR and SR-BI were detected in 34.6% and 36.5% of cases, respectively, with minimal overlap. These autoantigens function as negative regulators of endothelial activation and T cell differentiation, and autoantibodies block the functions of their targets, thereby contributing to the maintenance of vascular inflammation. Anti-EPCR autoantibodies were also detected in 80% of ulcerative colitis (UC), which is genetically and clinically associated with TAK. Same autoantibodies in inflammatory diseases with different target organs imply a common underlying pathophysiology such as intestinal dysbiosis, of these diseases, which would be linked to the aberrant activation of B cells.

Free Research Field

リウマチ膠原病内科

Academic Significance and Societal Importance of the Research Achievements

本研究課題の対象である、自己抗体、細胞内代謝、腸内細菌叢の検討は、血管炎症候群での検討がほとんど行われておらず、それ自体の新規性が高いが、本研究の中心となる自己抗体は申請者が世界に先駆けて報告しており、独自性が非常に高い。更に、血管炎症候群と潰瘍性大腸炎の合併についてはこれまで認識はされているものの、両疾患が共通の病態背景を有する疾患であるとの実証や仮説としての報告はない。これらの研究から推測される病態解明は、血管炎症候群と炎症性腸疾患研究において、極めて斬新な内容でかつ新規疾患概念の提唱も目標となるため極めて創造性が高いと考えられる。