Comprehensive analysis of serum peptides for exploration of novel biomarkers and therapeutic targets of microscopic polyangiitis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07926
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Kurokawa Manae 聖マリアンナ医科大学, 医学研究科, 教授 (90301598)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 顕微鏡的多発血管炎 / バイオマーカー / 血清ペプチド / 質量分析 / 治療標的

Outline of Final Research Achievements

As novel serum peptide biomarker candidates for microscopic polyangiitis (MPA), we identified a complement C4-derived peptide (1,738 m/z) and an unknown peptide (2,503 m/z) in addition to AC13, an apolipoprotein A-I-derived peptide (1,525 m/z). Injection of AC13 into SCG/ThpNkc mice, a model for ANCA-associated vasculitis, showed earlier onset of severe hematuria (p<0.05) and a tendency of higher crescent formation in glomeruli compared to the PBS-injection. Taken together the result that AC13 induces inflammatory cytokines of IL-6 and IL-8, the peptide is considered to be involved in exaggeration of the pathophysiology of MPA. We also screened 37kD protein as a candidate receptor for AC13. This study revealed multiple serum peptide biomarkers for MPA, and that AC13, a bioactive peptide, may be not only a useful biomarker but also a therapeutic target for MPA.

Free Research Field

リウマチ・膠原病

Academic Significance and Societal Importance of the Research Achievements

ANCA関連血管炎は、欧米では多発血管炎性肉芽腫症（GPA）の頻度が高いが、本邦ではMPAの方が高頻度で患者数も増加しており、MPA特異的なバイオマーカーの確立及び治療標的分子の解明が急務である。現在MPO-ANCAがMPAの診断に用いられるが、これはGPAや 好酸球性多発血管炎性肉芽腫症（EGPA）等でも認められ、MPAと他血管炎との鑑別を困難にしている。我々が同定したAC13、補体C4由来ペプチド、新規ペプチドの中で、特にAC13はGPAやEGPAを含む他疾患では認めず腎炎病態を増悪させたことから、MPO-ANCAを凌駕するMPAのバイオマーカーかつ治療標的となることが期待される。