The discovery and the clinical significance of autoantibodies against fibroblast activation proteins in interstitial lung disease

作者：Junqi Li, Huimin Huang, Qi Fang, Yuan Lyu, Gaojie Bai, Yu Xiao, Xiaomin Peng, Jiani Liu, S. Wang, Miao Shi, Simin Zhao, Zhenli Fu, Lei Zhang, Jiangtian Yu, Qun Luo, Lei Zhang, Xinjun Wang, Xinlu Wang, Baoqing Sun, Penghui Yang, Jin Su · 发表于：European journal of medical research · 年份：2026 · DOI：10.1186/s40001-026-04404-x · 研究领域：Peptidase Inhibition and Analysis、Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Antifungal resistance and susceptibility

Interstitial lung disease (ILD) was a chronic, progressive, and irreversible fibrotic condition associated with high mortality. Current standard diagnosis relied primarily on invasive modalities such as high-resolution computed tomography (HRCT) and biopsy, highlighting the urgent need for a noninvasive and accurate screening approach. Fibroblast activation protein (FAP) was highly expressed in activated fibroblasts but minimally detected in quiescent normal fibroblasts; however, the presence of FAP-specific autoantibodies in serum and their potential association with ILD pathogenesis remained unreported. This study aimed to describe the first identification of FAP autoantibodies in the serum of ILD patients and evaluate their potential as novel blood-based biomarker for ILDs. Multiple complementary assays were used to detect FAP autoantibodies, including enzyme-linked immunosorbent assay (ELISA), western blotting, immunofluorescence staining, and flow cytometry. Chemiluminescence immunoassay was employed to measure the epithelial injury marker Krebs von den Lungen-6 (KL-6). Additionally, 18 F-FAPI-04 positron emission tomography/computed tomography (PET/CT) imaging was performed to assess FAP-related signal intensity in ILD lesions, and the clinical trial registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ , ChiCTR-IPR-2100045352) at 13 April 2021. We identified FAP autoantibodies in the serum of ILD patients and COVID-19 patients for the first time...