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-DR low 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 (= - 0.2, p=0.02).
European Respiratory Journal published a clinical update in Critical Care on 07 May 2026.
The item focuses on The transcriptome of CD14+CD163-HLA-DRlow monocytes predicts mortality in idiopathic pulmonary fibrosis.
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