Pathogenetic role of ectopic lymphoid organs formed in IgG4-related vascular lesions

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08504
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Department of Clinical Research, National Hospital Organization Kanazawa Medical Center
• Principal Investigator: Kasashima Fuminori 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): 2020-04-01 – 2023-03-31
• Keywords: IgG4-related disease / IgG4-AAA / follicular helper T cell / reguratory T cell / Tertiary lymphoid organs

Outline of Final Research Achievements

IgG4-AAA (typical IgG4-related vascular disease) was characterized by numerous, large, irregular-shaped arterial tertiary lymphoid organs(ATLOs), and higher numbers of Tfr and Tfh2 cells than Tfh1 cells were present compared to patients with other vascular diseases. The morphological abnormalities (in number, area, and form) of ATLOs in IgG4-AAA and the increased number of Tfr cells are closely related to the activity of IgG4-related disease, including the number of IgG4-positive plasmacytes and the degree of adventitial thickness. An increase in Tfr cells in IgG4-AAA was associated with ATLO formation. Increased Tfh17 cells were found in TKA, and aAAA and non-IgG4-IAAA were characterized by increased Tfh1 cells．IgG4-AAA should be positioned as adventitial vasculitis with predominant Tfr and Tfh2 cells, accompanied by the abnormal appearance of ATLOs.

Free Research Field

血管外科学

Academic Significance and Societal Importance of the Research Achievements

IgG4関連血管病変（IgG4-VD）は,血清IgG4高値や動脈外膜を中心としたIgG4陽性細胞浸潤を特徴とする炎症性動脈病変の新しい疾患概念である．IgG4-VDでは組織学的診断が困難な例があり,より確実な診断指標が求められている．本研究では，IgG4-VDにおけるTfr, Tfh2優位のT細胞サブセットは異常ATLOs形成およびIgG4-RDの活動性に関連する事が示唆された．IgG4-VDに特徴的なT細胞サブセットおよび形態学的に不整なATLOsは今後の組織診断においても有用である．