Functional and pathophysiology analysis of anti-MDA5 antibody

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K15433
• 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: Juntendo University
• Principal Investigator: Yoshiyuki Abe 順天堂大学, 医学部, 助教 (10647027)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 抗MDA5抗体 / 動物実験モデル / 血漿交換療法 / 急速進行性間質性肺炎

Outline of Final Research Achievements

"Anti-MDA5 (Melanoma differentiation-associated gene 5) antibody-positive rapidly progressive interstitial pneumonia", a disease in which a new treatment was reported in 2013 and the 2-year survival rate improved from 28.6% to 75%, improved. However, it is a disease with a poor prognosis in which 25% of patients show treatment resistance and die early 6 months after the onset. We have succeeded in developing a new treatment method called "simple plasma exchange therapy" by retrospective clinical research for this fatal disease, and we have induced a completely new anti-MDA5 antibody that is unprecedented in the world as basic medical research. Succeeded in creating an interstitial pneumonia model mouse (Japanese Patent Laid-Open No. 2021-100388 Method for producing an interstitial pneumonia model non-human animal).

Free Research Field

膠原病内科学

Academic Significance and Societal Importance of the Research Achievements

新規治療方法の確立により、我々は生存率25%であった治療抵抗性の抗MDA5抗体陽性急速進行性間質性肺炎の1年生存率を92%まで上昇させた。より洗練された治療法の確立のため動物モデルマウスの開発に着手し、患者血清から抽出されたIgGをマウスに投与することで間質性肺炎を誘導することに成功した。これにより患者血清に含まれるIgGに病原性があることが明らかとなり、実臨床における治療戦略において大きな成果を得た。並行して観察臨床研究を行っており、間質性肺炎再燃症例は全例抗体価が上昇していることが明らかとなった。