New research reveals a specific immune cell profile that can strongly predict mortality in patients who have idiopathic pulmonary fibrosis (IPF). The study, “The Transcriptome of CD14+CD163-HLA-DRlow Monocytes Predicts Mortality in Idiopathic Pulmonary Fibrosis,” was published in European Respiratory Journal.
Using single-cell RNA sequencing, researchers analyzed lung tissue, peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage (BAL) fluid of more than 1,000 individuals, of which 555 had IPF. They discovered that a subset of immune cells — CD14+CD163−HLA-DRlow monocytes — was associated with poor outcomes.
The team identified elevated expression of pro-fibrotic, pro-angiogenic and chemotactic factors in these monocytes, which suggests an active correlation to disease progression and lung scarring. The unique 230-gene signature also correlated with fibrosis-associated macrophage profiles in lung tissue, indicating an expansion of immune dysfunction in the disease.
Researchers confirmed that IPF patients with high levels on CD14+CD163−HLA-DRlow monocytes had higher rates of mortality, decreased lung function as measured by forced vital capacity (FVC) and weakened manifestation of T-cell co-stimulatory genes. Further, patients with progressive IPF had almost double the amount of high-risk monocytes compared to patients with stable IPF.
Following their findings, the researchers posited specific drug classes that could possibly modify the high-risk gene signature. A faction of six genes, in particular, preserved predictive performance across several patient cohorts, the authors noted.
The study highlights the use of immune-cell-based transcriptomic profiling to aid IPF diagnosis and targeted precision medicine to treat the disease. The authors said future clinical trials can validate the targets and assess possible interventions to improve survival rates of high-risk IPF patients.
