Publication Date

7-1-2023

Journal

Journal of Extracellular Biology

DOI

10.1002/jex2.98

PMID

38939072

PMCID

PMC11080873

PubMedCentral® Posted Date

7-13-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

and nonspecific interstitial pneumonia (NSIP), biomarker, chronic hypersensitivity pneumonitis (CHP), differential diagnosis, ELISA, extracellular vesicles, idiopathic pulmonary fibrosis (IPF), interstitial lung diseases, lasso regression, mass spectrometry, noninvasive diagnosis, proteomics, usual interstitial pneumonia (UIP)

Abstract

High-resolution computed tomography (HRCT) imaging is critical for diagnostic evaluation of Idiopathic Pulmonary Fibrosis (IPF). However, several other interstitial lung diseases (ILDs) often exhibit radiologic pattern similar to IPF on HRCT making the diagnosis of the disease difficult. Therefore, biomarkers that distinguish IPF from other ILDs can be a valuable aid in diagnosis. Using mass spectrometry, we performed proteomic analysis of plasma extracellular vesicles (EVs) in patients diagnosed with IPF, chronic hypersensitivity pneumonitis, nonspecific interstitial pneumonitis, and healthy subjects. A five-protein signature was identified by lasso regression and was validated in an independent cohort using ELISA. The five-protein signature derived from mass spectrometry data showed an area under the receiver operating characteristic curve of 0.915 (95%CI: 0.819-1.011) and 0.958 (95%CI: 0.882-1.034) for differentiating IPF from other ILDs and from healthy subjects, respectively. Stepwise backwards elimination yielded a model with 3 and 2 proteins for discriminating IPF from other ILDs and healthy subjects, respectively, without compromising diagnostic accuracy. In summary, we discovered and validated EV protein biomarkers for differential diagnosis of IPF in independent cohorts. Interestingly, the biomarker panel could also distinguish IPF and healthy subjects with high accuracy. The biomarkers need to be evaluated in large prospective cohorts to establish their clinical utility.

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