# Serum vesicle biomarkers reflect the disease activity of idiopathic pulmonary fibrosis

## TL;DR

This study identifies serum vesicle biomarkers, including SFTPB, that reflect disease activity in idiopathic pulmonary fibrosis (IPF), offering potential for better disease monitoring.

## Contribution

The study discovers SFTPB as a novel, lung-specific biomarker in serum extracellular vesicles that correlates with IPF progression and disease activity.

## Key findings

- Serum extracellular vesicles captured heterogeneous fibrotic profiles in IPF patients.
- SFTPB showed superior diagnostic performance and was associated with progressive disease activity.
- SFTPB was linked to the TGF-β/SMAD pathway in SCGB3A2 + cells in IPF lungs.

## Abstract

Idiopathic pulmonary fibrosis (IPF) is a heterogeneous disease caused by an interplay of genetic and environmental factors. Biomarkers that reflect the progression of fibrosis are required for the management of IPF.

We extracted serum extracellular vesicles from a discovery cohort (127 IPF patients and 34 controls) and a validation cohort (20 IPF patients and 22 controls). Non-targeted proteomic analysis was performed by a data-independent acquisition method. We investigated the proteomic profiles in relation to multiple clinical parameters associated with IPF. To further evaluate the biological relevance of the identified biomarkers, we analyzed publicly available single-cell RNA sequencing datasets of lung tissue and conducted immunochemical validation using our collected lung samples.

We obtained 2420 protein profiles in serum extracellular vesicles and identified 19 IPF-associated proteins; their expressions were significantly lung-specific. Protein module analyses revealed that the upstream components of the complement system were increased in IPF. These IPF-associated proteins were involved in various IPF-associated genes and heterogeneously increased in IPF patients. Notably, surfactant protein B (SFTPB) not only showed superior diagnostic performance over the existing marker but was also significantly associated with progressive disease activity, such as the extent of fibrosis and decline in lung function. Furthermore, single-cell RNA-sequencing analysis revealed that SFTPB was associated with the TGF-β/SMAD pathway in SCGB3A2 + cells in IPF lungs. SFTPB expression in SCGB3A2 + cells was confirmed by immunostaining.

Serum extracellular vesicles could capture heterogenetic fibrotic profiles in IPF, and SFTPB can be a promising biomarker reflecting the disease activity.

The online version contains supplementary material available at 10.1186/s12967-025-07011-2.