S100A9/CD163 expression profiles in classical monocytes as biomarkers to discriminate idiopathic pulmonary fibrosis from idiopathic nonspecific interstitial pneumonia

<jats:title>Abstract</jats:title><jats:p>Circulating monocytes have pathogenic relevance in idiopathic pulmonary fibrosis (IPF). Here, we determined whether the cell surface levels of two markers, pro-inflammatory-related S100A9 and anti-inflammatory-related CD163, expressed on CD14<jats:sup>strong</jats:sup>CD16<jats:sup>−</jats:sup> classical monocytes by flow cytometry could discriminate IPF from idiopathic nonspecific interstitial pneumonia (iNSIP). Twenty-five patients with IPF, 25 with iNSIP, and 20 healthy volunteers were prospectively enrolled in this study. The S100A9<jats:sup>+</jats:sup>CD163<jats:sup>−</jats:sup> cell percentages in classical monocytes showed a pronounced decrease on monocytes in iNSIP compared to that in IPF. In contrast, the percentages of S100A9<jats:sup>−</jats:sup>CD163<jats:sup>+</jats:sup> cells were significantly higher in iNSIP patients than in IPF patients and healthy volunteers. In IPF patients, there was a trend toward a correlation between the percentage of S100A9<jats:sup>+</jats:sup>CD163<jats:sup>−</jats:sup> monocytes and the surfactant protein-D (SP-D) serum levels (<jats:italic>r</jats:italic> = 0.4158, [95% confidence interval (CI) − 0.02042–0.7191], <jats:italic>p</jats:italic> = 0.051). The individual percentages of S100A9<jats:sup>+</jats:sup>CD163<jats:sup>−</jats:sup> and S100A9<jats:sup>−</jats:sup>CD163<jats:sup>+</jats:sup> cells were also independently associated with IPF through multivariate regression analysis. The unadjusted area under the receiver operating characteristic curve (ROC-AUC) to discriminate IPF from iNSIP was (ROC-AUC 0.802, 95% CI [0.687–0.928]), suggesting that these are better biomarkers than serum SP-D (<jats:italic>p</jats:italic> < 0.05). This preliminary study reports the first comparative characterization of monocyte phenotypes between IPF and iNSIP.</jats:p>