elucidation of the mechanism of lung fibrosis with hypersensitivity pneumonitis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K20895
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Furusawa Haruhiko 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (40632154)
• Project Period (FY): 2021-08-30 – 2024-03-31
• Keywords: 過敏性肺炎 / 遺伝子解析

Outline of Final Research Achievements

Hypersensitive Pneumonitis (HP) is a diffuse lung disease caused by the repeated inhalation and sensitization of antigens. A subset of HP patients, who experience continuous antigen exposure, develop fibrotic HP. This study aims to identify the risk genes associated with HP and elucidate how these genes contribute to the clinical manifestations of the disease. In non-Hispanic white HP patients, the genes TERC, DSP, MUC5B, and IVD were found to be associated with fibrosis. Subsequently, a genome-wide association study (GWAS) was conducted on Japanese HP patients, comparing their data with that of healthy controls. We are currently investigating the susceptibility genes for the disease.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

HP は抗原の反復吸入および感作によって生じるびまん性肺疾患であり、線維性HPは特発性肺線維症（idiopathic pulmonary fibrosis; IPF）と類似した病態と経過を辿る予後不良な疾患であり、IPFとの鑑別が問題となる。一方で原因抗原に持続曝露された人の中でHP発症に至るのは 4～20％程度であり、また発症したHPのなかで線維化が進展する症例は1/2～1/3程度であるため、原因抗原の同定や予後予測は困難である。発症や予後を規定する遺伝子を同定することで、IPFとの鑑別や早期治療介入、また重症化を予測して肺移植や抗線維化薬の導入などを早期に行うことができると考えられる。