American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Aug 2024
Single-Cell Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis.
Rationale: Changes in peripheral blood cell populations have been observed, but not detailed, at single-cell resolution in idiopathic pulmonary fibrosis (IPF). Objectives: We sought to provide an atlas of the changes in the peripheral immune system in stable and progressive IPF. Methods: Peripheral blood mononuclear cells (PBMCs) from patients with IPF and control subjects were profiled using 10× chromium 5' single-cell RNA sequencing. ⋯ The fraction of Tregs out of all T cells was also increased in two cohorts of lung single-cell RNA sequencing. CCL22 and CCL18, ligands for CCR4 and CCR8 Treg chemotaxis receptors, were increased in IPF. Conclusions: The single-cell atlas of the peripheral immune system in IPF reveals an outcome-predictive increase in classical monocytes and Tregs, as well as evidence for a lung-blood immune recruitment axis involving CCL7 (for classical monocytes) and CCL18/CCL22 (for Tregs).
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Am. J. Respir. Crit. Care Med. · Aug 2024
Machine Learning of Plasma Proteomics Classifies Diagnosis of Interstitial Lung Disease.
Rationale: Distinguishing connective tissue disease-associated interstitial lung disease (CTD-ILD) from idiopathic pulmonary fibrosis (IPF) can be clinically challenging. Objectives: To identify proteins that separate and classify patients with CTD-ILD and those with IPF. Methods: Four registries with 1,247 patients with IPF and 352 patients with CTD-ILD were included in analyses. ⋯ Conclusions: Multiple machine learning models trained with large cohort proteomic datasets consistently distinguished CTD-ILD from IPF. Many of the identified proteins are involved in immune pathways. We further developed a novel approach for single-sample classification, which could facilitate honing the differential diagnosis of ILD in challenging cases and improve clinical decision making.