Blood levels of soluble macrophage-mannose receptor (sCD206) are uniquely associated with severity and mortality in idiopathic pulmonary fibrosis

<bold>Objectives:</bold> Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease driven by pro-fibrotic pulmonary macrophages expressing the macrophage mannose receptor CD206. Recently, blood levels of soluble CD206 (sCD206) have been found to be associated with IPF severity and mortality. This study aimed to confirm this association in a large validation cohort and to investigate the uniqueness of sCD206 as an IPF biomarker by comparing it to two other macrophage biomarkers. <bold>Materials & Methods:</bold> Macrophage biomarkers (sCD206, sCD163 and sSIRPα) were assessed in blood samples from 150 patients with IPF at baseline, and after 12 and 36 months using the enzyme-linked immunosorbent assay (ELISA) method. <bold>Results:</bold> The level of the three biomarkers was stable and within normal ranges at baseline, and after 12 and 36 months. Contrary to sCD163 and sSIRPα, sCD206 demonstrated repeated significant correlations to routine biochemical parameters (lactate dehydrogenase, p=0.0096; albumin, p=0.0027; haemoglobin, p=0.0141; C-reactive protein, p=0.0004) at baseline. Higher levels of sCD206 were significantly associated with poorer results for the 6-minute walking test, forced vital capacity and shortness of breath (p=0.0002, p=0.0182 and p=0.0199, respectively). Mortality was significantly increased (p=0.0030) in patients with sCD206 >0.357 mg/L at baseline. <bold>Conclusion:</bold> The macrophage biomarker sCD206 is uniquely associated with both IPF disease severity and mortality. The functional role of CD206+ macrophages in IPF and the diagnostic potential of sCD206 should be further investigated.