Prognostic factors of IgG4-related vascular disease

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10773
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: Kanazawa University
• Principal Investigator: Kasashima Satomi 金沢大学, 保健学系, 准教授 (20444200)
• Co-Investigator(Kenkyū-buntansha): 尾崎 聡 金沢大学, 保健学系, 助教 (40401921) ; 川島 篤弘 独立行政法人国立病院機構(金沢医療センター臨床研究部), その他部局等, その他 (20242563) ; 笠島 史成 独立行政法人国立病院機構(金沢医療センター臨床研究部), その他部局等, その他 (90303304)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: IgG4関連疾患 / IgG4関連大動脈瘤 / 外膜肥厚 / matrix metalloproteinase

Outline of Final Research Achievements

MMP-9 production in various immune-cells of the adventitia was characteristic of IgG4-AAA and was highly associated with the activity of IgG4-AAA. MMPs expression in the adventitia of IgG4-AAA may be involved in lymphoid follicle formation and not only in the formation and progression of aneurysms, but also in the remodeling of the thick fibrous adventitia.
After intravascular treatment, among the IgG4-AAA, the IgG4-AAA-up group (serum IgG4 increasing after treatment) showed a preoperative high IL-6 and an increase of postoperative aneurysm diameter. Thus, the IgG4-AAA-up group was thought to be as a high-risk group with a progressive tendency. The IgG4-AAA-up group is characterized by high preoperative IgG4 / IgG ratio, high MMP-9, and high monocyte to eosinophil ratio. These indicators are candiate of prognostic factors for IgG4-AAA.

Free Research Field

IgG4関連疾患，血管炎

Academic Significance and Societal Importance of the Research Achievements

IgG4血管病変は,解離や瘤破裂等の急性の致死的合併症があり，緩徐な経過の他臓器IgG4関連疾患とは予後が大きく異なる．動脈硬化性大動脈瘤と比較して，進行が速い場合があり，治療方法の選択も慎重にすべきである．今回の研究では，今まで明らかにされていなかった大動脈外膜のMMPs産生が明らかになり，特にMMP-9の産生とIgG4関連疾患の活動性との関連が解明された．そのため，術前に，動脈硬化性大動脈瘤とIgG4血管病変を鑑別することの意義が明確となり，IgG4血管病変と診断された場合，治療方針の選択，進展や増悪の指標が明示され，IgG4関連血管病変患者の余命，予後予測に光明が得られた．