Noninvasive assessment of the lung inflammation-fibrosis axis by targeted imaging of CMKLR1

Philip Z Mannes ^1,2, Taylor S Adams ³, Samaneh Farsijani ^4,5

⁰Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.

Science Advances +

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June 19, 2024

View abstract on PubMed

Summary

Researchers identified CMKLR1 as a novel imaging biomarker for fibrotic lung diseases. This marker helps track lung inflammation and predict disease progression in idiopathic pulmonary fibrosis (IPF) patients.

Area Of Science

Pulmonary Medicine
Immunology
Biomarker Discovery

Background

Fibrotic lung diseases lack precise biomarkers for risk stratification and treatment monitoring.
Idiopathic pulmonary fibrosis (IPF) presents diverse clinical courses, complicating management.

Purpose Of The Study

To validate CMKLR1 as an imaging biomarker for the lung inflammation-fibrosis axis.
To assess CMKLR1's role in identifying disease endotypes and predicting outcomes in fibrotic lung diseases.

Main Methods

Single-cell RNA sequencing analysis of lung tissue.
In vivo studies using a murine model of bleomycin-induced lung fibrosis.
CMKLR1-targeted positron emission tomography (PET) imaging.
Analysis of bronchoalveolar lavage (BAL) cells from IPF patients.

Main Results

CMKLR1 expression is a transient signature of monocyte-derived macrophages (MDMφ) in IPF.
MDMφ are the primary cells taking up CMKLR1-targeting peptides in fibrotic lungs.
CMKLR1-targeted PET imaging quantifies lung inflammation and predicts fibrosis development in mice.
High CMKLR1 expression in BAL cells identifies an IPF subtype with poor survival.

Conclusions

CMKLR1 serves as a valuable imaging biomarker for assessing lung inflammation and fibrosis.
CMKLR1 facilitates endotyping and risk stratification in fibrotic lung diseases, particularly IPF.
This biomarker holds potential for improving patient management and therapeutic monitoring.