Identification of Biomarkers by Multiplex Suspension Array to Predict Progression in Patients with Idiopathic Interstitial Pneumonias

<bold>Objective:</bold> This study aim is to discover biomarkers that are indicative of idiopathic interstitial pneumonias progression. <bold>Method:</bold> Serum levels of 78 proteins in patients with idiopathic interstitial pneumonias were measured using a multiplex suspension array. Progression was defined as a greater than 10% decrease in FVC, greater than 15% decrease in DLCO, and developing acute exacerbation or death within 1 year post biomarker measurement. Biomarkers correlated with progression were determined using logistic regression analysis with a stepwise method. Existing single-cell RNA-sequencing data from the NCBI GEO database (GSE135893) were referenced to identify the cell source of biomarkers implicated in pulmonary fibrosis. <bold>Results:</bold> Among 142 patients, 58 ones (40.8%) experienced progression. Serum levels of CD30, TWEAK (TNFR superfamily proteins), TNF-R2, CCL5, and IL-1 receptor antagonist were independently associated with progression. Compared with single-cell RNA-sequencing data, CD30 was expressed in HAS1 high fibroblasts, which are implicated in pulmonary fibrosis. IL-1 receptor antagonist was expressed by macrophages, and CCL5 was expressed by T and NK cells. TWEAK was expressed in macrophages conventional dendritic cells. TNF-R2 was expressed in monocytes and proliferating T, NK, and plasmacytoid and conventional dendritic cells. <bold>Conclusion:</bold> This study identifies novel serum biomarkers potentially predictive of idiopathic interstitial pneumonias progression. These biomarkers, not previously reported, highlight their potential significance in early detection and intervention strategies in this disease.