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Updated: Jan 9, 2026
Quantification of Monocyte Transmigration and Foam Cell Formation from Individuals with Chronic Inflammatory Conditions
Published on: October 17, 2017
The transcriptome of CD14+CD163-HLA-DRlow monocytes predicts mortality in idiopathic pulmonary fibrosis
Theodoros Karampitsakos1,2, Minxue Jia3,4,2, Bochra Tourki1
1Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Ubben Center for Pulmonary Fibrosis Research, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Background:
The association between immune-cell-specific transcriptomic profiles and mortality in idiopathic pulmonary fibrosis (IPF) is unknown.
Methods:
We profiled peripheral blood mononuclear cells by single-cell RNA sequencing (scRNA-seq) and investigated which immune-cell-specific transcriptomic profile predicted IPF outcomes consistently. Prognostic accuracy was investigated in peripheral blood mononuclear cells (PBMCs), bronchoalveolar lavage (BAL) and lung tissue. Findings were validated by flow cytometry, analysis of independent scRNA-seq datasets and cellular deconvolution. We investigated the function of this transcriptomic profile and its cellular source in lung tissue (overall sample size, n=1054; IPF, n=555; other, n=499). Connectivity map analysis and LASSO regression were used to identify drug candidates and a subset of genes with prognostic potential, respectively.
Results:
A 230-gene up-score (Pittsburgh PBMC cohort) from CD14+CD163-HLA-DRlow monocytes predicted mortality in the Chicago PBMC cohort (HR 6.58, 95% CI 2.15-20.13; p=0.001), in BAL pooled analysis (HR 2.20, 95% CI 1.44-3.37; p=0.0003), and negatively correlated with forced vital capacity in lung tissues (ρ= -0.2, p=0.02). Proportions of CD14+CD163-HLA-DRlow monocytes were higher in progressive versus stable IPF (12.59%, 95% CI 9.66-16.23%, versus 7.61%, 95% CI 6.68-10.21%; p=0.014). High-risk patients with IPF had decreased expression of T-cell co-stimulatory genes (Pittsburgh and Chicago, p<0.01). CD14+HLA-DRlow monocytes had higher expression of profibrotic, proangiogenic and chemotactic factors compared to CD14+HLA-DRhi monocytes (p<0.05). The 230-gene up-score correlated with the secreted phosphoprotein 1 (SPP1)+ fibrosis-associated macrophages gene-score in lung tissues (ρ=0.19, p<2.2e-16). Connectivity map analysis identified drug categories to reverse the 230-gene signature. A subset of six genes retained predictive performance (pooled PBMC cohorts HR 4.79, 95% CI 2.58-8.92; p<0.0001).
Conclusions:
The transcriptome of CD14+CD163-HLA-DRlow monocytes is associated with increased mortality in patients with IPF. Its reversal should be investigated as a precision-based therapy in IPF.
Insights
A specific monocyte gene signature in idiopathic pulmonary fibrosis (IPF) patients predicts mortality. Targeting this signature may offer a novel precision therapy for IPF.
Area of Science:
- Immunology
- Pulmonary Medicine
- Genomics
Background:
- Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unknown prognostic biomarkers.
- The role of immune cell transcriptomes in IPF mortality remains unexplored.
Purpose of the Study:
- To identify immune-cell-specific transcriptomic profiles that predict mortality in IPF.
- To investigate the functional role and therapeutic potential of identified profiles.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMC), bronchoalveolar lavage (BAL), and lung tissue.
- Validation using flow cytometry, independent datasets, and cellular deconvolution.
- Gene expression analysis and connectivity mapping for drug discovery.
Main Results:
- A 230-gene signature in CD14+CD163-HLA-DRlow monocytes (Pittsburgh-PBMC) predicted mortality across multiple cohorts and correlated with reduced lung function.
- These monocytes were more abundant in progressive IPF and exhibited pro-fibrotic gene expression.
- A six-gene subset retained significant predictive power for IPF mortality.
Conclusions:
- The transcriptome of specific monocyte subsets is a significant predictor of mortality in IPF.
- Reversing this monocyte signature represents a potential precision-based therapeutic strategy for IPF.
