Clinical Application of Exosome KL-6 Detection in Respiratory Diseases

<bold>Objective:</bold> Krebs von den Lungen-6 (KL-6) is the unique biomarker of interstitial lung disease in the blood. The precursor of KL-6 is a membrane protein, which can be found in plasma exosomes. Therefore, whether the level of KL-6 in plasma exosomes could reflect lung injury more sensitively? <bold>Methods:</bold> In this study, 286 subjects were selected, with an average age of 61.5 years. The secretion and plasma KL-6 were detected by chemiluminescence method. In addition, the single-cell transcriptome data of pulmonary fibrosis diseases were also analyzed. <bold>Results:</bold> KL-6 (MUC1) was highly expressed in epithelial cells. The positive rates of exocrine KL-6 were 86.9% in interstitial lung disease group, 57.5% in lung cancer group, 54.8% in pneumonia group and 30.0% in airway disease group (P<0.01). The level of KL-6 in exosomes of interstitial lung disease [587.6(177.1,1620.4) U/mL] was significantly higher than that of other respiratory diseases and healthy controls (P < 0.01). The positive coincidence rate of exocrine KL-6 was significantly higher than that of plasma KL-6 (86.9% vs 70.5%, P < 0.01). The level of exocrine KL-6 is highly correlated with plasma KL-6 (R2= 0.930). The positive rates of plasma and exocrine KL-6 in each group were: 81.0% and 57.1% in interstitial pneumonia with autoimmune characteristics (P=0.018), 94.4% and 83.3% in idiopathic pulmonary interstitial fibrosis (P=0.066), and interstitial pneumonia associated with dermatomyositis. The signal-to-noise ratio of exosomes KL-6 was higher. <bold>Conclusion:</bold> There is a high correlation between exocrine KL-6 and plasma KL-6. Compared with plasma KL-6, exosome KL-6 is a more sensitive blood biomarker of lung injury.