Identification EXOSC4 as a novel autoantigen of interstitial lung disease in rheumatoid arthritis

作者：Chuanhui Yao, Xun Gong, Biyue Shang, Dan Dou, Weixiang Liu, Hui Xu, Yuchen Yang, Xieli Ma, Qiuwei Peng, Juan Jiao, Xiaopo Tang, Congmin Xia, Peng Chen, Quan Jiang · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-06667-0 · 被引用次数：9 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Monoclonal and Polyclonal Antibodies Research、Rheumatoid Arthritis Research and Therapies

BACKGROUND: Interstitial lung disease (ILD) is a common and severe comorbidity of rheumatoid arthritis (RA), yet reliable diagnostic biomarkers remain lacking. Alveolar type II (ATII) cells are widely recognized to play a key role in the pathogenesis of ILD. This study first aimed to screen and validate potential autoantigens involved in RA-ILD using ATII cells. METHODS: Sera from multiple patient groups were subjected to immunoprecipitation with ATII cells and analyzed for candidate autoantigens related to RA-ILD through proteomic methods. Antibody concentrations in the sera were subsequently measured using protein chips and ELISA. Expression levels of target antigens in the lung tissues of collagen-induced arthritis-bleomycin (CIA-BLM) mice were evaluated via immunohistochemistry, while their expression in ATII-BLM cells was assessed using indirect immunofluorescence. The diagnostic value of these antibodies was further examined by ROC curve analysis. Preliminary studies also explored the cellular mechanisms involved. RESULTS: We identified exosome component 4 (EXOSC4) as a potential autoantigen in RA-ILD, with significantly higher levels of EXOSC4 antibodies found in the sera of RA-ILD patients. Moreover, EXOSC4 expression was elevated in the lung tissues of CIA-BLM mice and in ATII-BLM cells. Clinical assessments showed that the area under the curve (AUC) for EXOSC4 antibody in diagnosing RA-ILD was 0.809, increasing to 0.890 (95% CI:0.812–0.967) when combined with other ...