Investigation of ageing-related production of MPO-ANCA

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19475
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: University of Tsukuba
• Principal Investigator: Nagai Kei 筑波大学, 医学医療系, 講師 (00734352)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 抗好中球細胞質抗体 / ミエロペルオキシダーゼ

Outline of Final Research Achievements

Vasculitis occurs in aged population and is caused by antibody against neutrophilic granule protein, myeloperoxidase (MPO-ANCA), in most asian countries including Japan. We comprehensively tested the level of expression of neutrophil cytoplasmic proteins and revealed highly expressed PTX3, contrary to reduced expression of representative neutrophilic protein such as MPO and PR3. We further examined the functional role of PTX3 in production of MPO-ANCA by an animal model with immunization of MPO and PTX3 at the same time. Under strictly limited condition, titer of MPO-ANCA was reduced comparing to the control group. This suggested the possibility of PTX3 as one of regulators of MPO-ANCA production and pathogenesis of AAV.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

AAVに対して従来からステロイド薬と免疫抑制薬の併用が治療の基本だが、真菌感染症などの日和見感染の合併が問題であり、新規治療法の開発が望まれている。MPO-ANCAはAAVの病因であり、その産生抑制は治療戦略の一つであるが、抗原たるMPOの欠損は真菌感染を増悪させる。他方、PTX3は日和見感染に防御的に機能することが既知であり、その臨床応用を見据える本研究は、これまでにない日和見感染合併症に配慮したAAVの治療法開発の意義を持つ。