Related Experiment Video
Updated: Aug 7, 2026
Robotic-assisted Bronchoscopy Combined with Multimodal Imaging for Targeted Lung Cryobiopsies
Published on: July 19, 2024
Targeted therapy against recurrent anti-synthetase syndrome associated interstitial lung disease after bilateral lung
Shiyao Wang1,2, Qingya Shi1,3, Wenxiu Xu1,2
1National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
Background:
Anti-synthetase syndrome (ASS) associated interstitial lung disease (ILD) usually responds to immunosuppressive therapy, but recurrence is common. We report a 58-year-old man with ASS-ILD who developed recurrent ILD within one year after bilateral lung transplantation (LTx). Despite triple immunosuppression (glucocorticoids, tacrolimus, mycophenolate mofetil), systemic inflammation persisted. This case represents an in vivo model of ASS-ILD recurrence, warranting further investigation into underlying mechanisms and novel therapeutic strategies.
Methods:
Peripheral blood mononuclear cells (PBMCs) were collected at 56 and 84 weeks post-transplant for single-cell RNA sequencing (scRNA-seq), while lung tissue was analyzed via spatial transcriptomics. Control data came from five naïve ASS-ILD patients and two clinically stable connective tissue disease associated ILD (CTD-ILD) patients post-LTx. Differential gene expression and pathway enrichment analyses were performed to identify therapeutic targets.
Results:
Exploratory PBMC scRNA-seq analysis suggested enrichment of interferon-, interleukin- and JAK-STAT-related signaling programs in circulating monocytes and neutrophils. Based on this immune activation profile, a multidrug treatment adjustment was implemented, including short-term glucocorticoid augmentation, replacement of mycophenolate mofetil with Janus kinase inhibitor tofacitinib, and replacement of tacrolimus with cyclosporine A. Following treatment adjustment, systemic inflammatory markers declined and interstitial lesions in both lungs were markedly alleviated on imaging. Subsequent spatial transcriptomic analysis of lung tissue revealed persistent interferon-related signaling and identified pro-fibrotic transcriptional programs in alveolar macrophages and transitional type II alveolar cells. Functional enrichment suggested a potential association between systemic inflammatory activation and localized fibrotic remodeling within the lung microenvironment.
Conclusions:
This case illustrates the potential utility of scRNA-seq and spatial transcriptomics for characterizing immune-related transcriptional programs in recurrent ASS-ILD after LTx. Transcriptomic profiling informed therapeutic decision-making in this complex clinical setting, and clinical improvement was observed following treatment adjustment. These findings generate exploratory insights into potential therapeutic targets in recurrent ASS-ILD.
