Development of clinical laboratory method for contribute to the evaluation of ANCA-related vasculitis

• Project/Area Number: 18K15386
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Nagoya University
• Principal Investigator: Kikuchi Ryosuke 名古屋大学, 医学部附属病院, 主任臨床検査技師 (30721435)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: VEGF-A / VEGF-A165b / ANCA / 血管炎 / ANCA関連血管炎 / 病態検査学 / 心血管病

Outline of Final Research Achievements

This study evaluated the clinical associations of serum vascular endothelial growth factor-A (sVEGF-A) and sVEGF-A165b concentrations with time to remission of AAV in a nationwide Japanese prospective follow-up cohort. Results revealed significant reductions in sVEGF-A and sVEGF-A165b concentrations in patients with microscopic polyangiitis and EGPA, respectively. However, despite the comparable concentrations of sVEGF-A and sVEGF-A165b during the 6 months of treatment in granulomatosis with polyangiitis patients, correlation analysis revealed that the differences in log2-transformed concentrations of sVEGF-A and sVEGF-A165b were inversely correlated with time to remission in granulomatosis with polyangiitis patients.These results suggest that sVEGF-A and -A165b can serve as potential markers of time to remission in patients with granulomatosis with polyangiitis.

Academic Significance and Societal Importance of the Research Achievements

これまでにANCA関連血管炎について、VEGF-Aの「作用変化」の側面からのアプローチは皆無であった。本研究は、VEGF-Aの「作用変化」とANCA関連血管炎との関連を明らかにすることであった。本研究を通して、ANCA関連血管炎の診断・活動性評価・再燃予測の有効なバイオマーカーの提供と将来的な治療ターゲットとなりうる分子機構解明への新たな概念を提供することを目的とした。研究成果として、sVEGF-Aおよび-A165bは、多発血管炎性肉芽腫症患者の寛解までの期間を示すマーカーとなりうることが示唆された。今後より詳細な解析を行うことでANCA関連血管炎の寛解予測ロジックを確立できる可能性がある。

Research Products

• [Journal Article] Vascular endothelial growth factor (VEGF)-A and VEGF-A165b are associated with time to remission of granulomatosis with polyangiitis in a nationwide Japanese prospective cohort study (2020)
  • Author(s): Kikuchi R、Tsuboi N、Sada K、Nakatochi M、Yokoe Y、Suzuki A、Maruyama S、Murohara T、Matsushita T、Amano K、Atsumi T、Takasaki Y、Ito S、Hasegawa H、Dobashi H、Ito T、Makino H、Matsuo S、Research Committee of Intractable Vasculitis Syndrome and Research Committee of Intractable
  • Journal Title: Annals of Clinical Biochemistry: International Journal of Laboratory Medicine Volume: 58 Issue: 2 Pages: 86-94
  • DOI: 10.1177/0004563220968371
  • Peer Reviewed / Open Access
• [Presentation] The Change for Qualitative Balance of Vascular Endothelial Growth Factor-A May Contribute to Therapeutic Efficacy for an Anti-Neutrophil Cytoplasmic Antibody Associated Vasculitis Subtypes. (2020)
  • Author(s): Ryosuke Kikuchi, Naotake Tsuboi, Shoichi Maruyama, Toyoaki Murohara, Tadashi Matsushita
  • Organizer: XXIV IFCC World Lab 2020
  • Int'l Joint Research
• [Presentation] VEGF-Aの質に着目したANCA関連血管炎の治療効果評価に寄与する評価法構築に向けて (2019)
  • Author(s): 菊地良介、坪井直毅、丸山彰一、室原豊明、松下正
  • Organizer: 第66回日本臨床検査医学会学術集会
• [Remarks] 名古屋大学医学部附属病院 医療技術部 臨床検査部門
  • URL: https://www.med.nagoya-u.ac.jp/labmed/index.html