Evaluation of alterations in post-translational modification of autoantigens as a novel early phase diagnostic marker for ANCA associated vasculitis.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08998
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Kindai University
• Principal Investigator: Nagai Kouhei 近畿大学, 生物理工学部, 准教授 (70500578)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 自己免疫疾患 / ANCA関連血管炎 / 自己抗原 / 翻訳後修飾 / 膠原病 / 質量分析

Outline of Final Research Achievements

In this study, we analyzed post-translational modifications (PTMs) of autoantigen Myeloperoxinase (MPO) in peripheral blood neutrophils from patients with ANCA-related vasculitis. Neutrophil MPO was purified from peripheral blood of 8 patients with ANCA-related vasculitis and 8 healthy controls, digested with trypsin, and analyzed by high-performance LC-MS. Database search against human proteome database identified 52 PTMs on the MPO molecules. Among them, multiple post-translational modifications such as Carbamylation were significantly increased in the patient group. Furthermore, the immunization of mice with a post-translational modification-introduced mouse protein causes a temporary increase in the antibody titer against the self-protein. These results indicated the relationship between abnormal post-translational modification and autoantibody production.

Free Research Field

プロテオミクス

Academic Significance and Societal Importance of the Research Achievements

本研究では、ANCA関連血管炎患者の体内の自己抗原タンパク質Myeloperoxidase（MPO）上に、患者特異的な翻訳後修飾が存在することを初めて示した。更に、自己タンパク質の翻訳後修飾の異常が自己抗体を誘導しうることをマウスを用いた実験により示した。本研究成果は、ANCA関連血管炎における疾患発症機序の解明に寄与するだけでなく、MPOにおける患者特異的翻訳後修飾が、自己抗体の産生に先駆ける現象として、ANCA関連血管炎の早期診断マーカーとして使用できる可能性を示したということで大きな社会的意義を有していると考える。