Establishment of a quantitative system for AC13, a candidate for a novel serum peptide biomarker of microscopic polyangiitis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07392
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Sato Masaaki 聖マリアンナ医科大学, 医学部, 助教 (90463801)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: バイオマーカー / 顕微鏡的多発血管炎

Outline of Final Research Achievements

AC13, a peptide of C-terminal 13 amino acid residues of apolipoprotein A-I which is specifically increased in the sera of patients with active phase of microscopic polyangiitis (MPA). In this study, we have established a measurement system for AC13 by mass spectrometry using stable isotope-labeled AC13 as an internal standard. Serum AC13 concentration in MPA were significantly higher than those in granulomatosis with polyangiitis, rheumatoid arthritis, and healthy subjects. Serum AC13 concentration showed a strong positive correlation with CRP, suggesting the involvement of AC13 in the inflammation of MPA. We also obtained an anti-AC13 monoclonal antibody-producing hybridoma line which is required for measurement of serum AC13 concentration by competitive ELISA. These measurement systems of serum AC13 concentration may provide a clinical laboratory examination useful for differential diagnosis of MPA from related diseases.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

AC13は、MPAを近縁疾患から鑑別できる初の血液バイオマーカーとなる可能性が高い。本研究で構築した定量系は、症候の有無や医師の判断の差に関わらない均一な診断を可能とするため、有用な臨床検査項目となり得る。本研究で定量した血清AC13濃度はCRPと強い正の相関を示したため、血清AC13濃度が高い患者では炎症性サイトカインの産生亢進による炎症促進や、アポリポ蛋白A-I切断酵素が炎症時に活性化していることが示唆される。AC13はMPAのバイオマーカーとなるだけでなく、アポリポ蛋白A-I切断酵素やAC13シグナル伝達経路を同定することにより、MPAにおける治療標的となる可能性がある。