A NEW study has identified a specific immune cell profile that strongly predicts mortality in patients with idiopathic pulmonary fibrosis (IPF), a progressive and often fatal lung disease. Researchers used single-cell RNA sequencing (scRNA-seq) to analyse peripheral blood mononuclear cells (PBMCs), bronchoalveolar lavage (BAL) fluid, and lung tissue from more than 1,000 individuals, including 555 with IPF.
High-Risk Monocytes in Idiopathic Pulmonary Fibrosis
The team discovered that CD14+CD163−HLA-DRlow monocytes, a subset of immune cells, carry a distinctive 230-gene signature associated with poor outcomes. Patients with high levels of these monocytes had significantly higher mortality rates, reduced lung function as measured by forced vital capacity (FVC), and decreased expression of key T-cell co-stimulatory genes. Progressive IPF patients had nearly double the proportion of these high-risk monocytes compared with stable cases.
These CD14+HLA-DRlow monocytes were found to express elevated levels of pro-fibrotic, pro-angiogenic, and chemotactic factors, suggesting they actively contribute to lung scarring and disease progression. The 230-gene signature also correlated with fibrosis-associated macrophage profiles in lung tissue, highlighting a broader network of immune dysfunction in IPF.
Importantly, researchers identified existing drug classes that could potentially reverse this high-risk gene signature. A refined panel of six genes retained strong predictive power across multiple patient cohorts, offering a possible avenue for precision medicine interventions.
Towards Targeted Treatments
The findings underscore the potential of immune-cell-based transcriptomic profiling to guide prognosis and therapy in IPF. By targeting the pathways active in CD14+CD163−HLA-DRlow monocytes, clinicians may be able to develop precision-based treatments aimed at slowing or halting disease progression. Future studies will need to validate these targets in clinical trials and explore how interventions could improve survival for high-risk IPF patients.
This research provides a critical step toward personalised management of IPF, giving healthcare professionals a clearer understanding of which patients are most at risk and how targeted therapies could reshape outcomes.
Reference
Karampitsakos T et al. The transcriptome of CD14+CD163–HLA-DRlow monocytes predicts mortality in idiopathic pulmonary fibrosis. Eur Respir J. 2025; DOI:10.1183/13993003.00804-2025.
