Diagnostic and therapeutic approach for sporadic inclusion body myositis via identification of pathomechanism of the autoantibodies.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07870
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: International University of Health and Welfare (2022); Kumamoto University (2020-2021)
• Principal Investigator: YAMASHITA Satoshi 国際医療福祉大学, 国際医療福祉大学成田病院, 教授 (20457592)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 封入体筋炎 / cN1A / 能動免疫 / マウスモデル

Outline of Final Research Achievements

Autoantibodies against cytosolic 5’-nucleotidase 1A (cN1A) were found in the sera of patients with sporadic inclusion body myositis (sIBM). However, the pathogenic role of the autoantibodies remained unknown. This study investigated the differences in clinical features between sIBM patients with and without the autoantibodies, and the pathogenic properties of the autoantibodies using active cN1A peptides immunization. Among 365 patients classified as sIBM, 201 (55.1%) patients were positive for anti-cN1A antibodies. Patients positive for anti-cN1A antibodies revealed significant differences in finger flexion weakness frequency, and absolute values between grip strength of both hands. The number of myofibers with internal nuclei increased in all the peptide-injected groups, with surrounding or invading CD8-positive T cells into myofibers, aggregates, and p62 and LC3 upregulation. Active cN1A peptide immunization reproduces clinicohistological sIBM aspects in wild-type mice.

Free Research Field

脳神経内科学

Academic Significance and Societal Importance of the Research Achievements

封入体筋炎（sIBM）は、50歳以上の患者で最も多い炎症性筋疾患であり、本邦でもその患者数は増加傾向にある。本症に有効な治療法はなく、本質的な病態の理解と疾患モデルの確立は喫緊の課題である。抗cN1A抗体陽性患者は、手指屈曲優位の筋力低下を伴うことが多く、本抗体がsIBMの臨床病理学的特徴の修飾因子となる可能性が示された。また、cN1Aペプチドの能動免疫によりsIBMの炎症および変性面の特徴が再現され、抗cN1A抗体が病態メカニズムにおいて重要な役割を果たすことが示唆された。本モデルは、sIBMの病態を解明し、新たな治療戦略の開発に有用である。