Investigation of Disease Activity-Related Factors in Giant Cell Arteritis Using Peripheral Blood RNA-seq

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16283
• 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: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: Kobayashi Satomi 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (20897201)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 巨細胞性動脈炎 / RNA-sequencing

Outline of Final Research Achievements

Giant cell arteritis (GCA), predominantly affecting the elderly, is an autoimmune large-vessel vasculitis classified as an intractable disease. This study aimed to identify gene groups associated with disease activity and pathophysiology in GCA by performing RNA sequencing on whole blood samples. Thirty-four GCA samples and 14 age- and sex-matched non-disease control samples were analyzed using various methods of dimensional reduction and gene enrichment analysis. The results revealed that the expression of specific transcription factor-related genes was downregulated in initial onset/relapse GCA groups compared to stable GCA/non-disease control groups. This gene signature tended to be low in GCA groups with a history of recurrence.

Free Research Field

膠原病・リウマチ学

Academic Significance and Societal Importance of the Research Achievements

GCA診療の課題に病勢指標の不足、患者層別化と各治療最適化の欠如、抗IL-6治療下再燃例の新規治療選択肢の不足が挙げられる。本研究では初発時/再燃時GCAと安定時GCAで発現パターンが異なった遺伝子群から、病勢指標候補の抽出、臨床パラメータとの関連検索を行い、最適な病勢指標を抽出することを目指す。またGCAの大型血管型/頭頚部型などのサブグループでの発現データの違いを抽出し、最終的に各タイプに適切な治療を確立するためのデータを蓄積する。さらに抗IL-6治療下に再燃した症例のデータの特徴を抽出することで、新しい治療標的の探索に資するものと考えられる。