Circulating exosomes revealing dysregulated pathways in pulmonary sarcoidosis: first results of PULSAR-CLIMB study

<bold>Introduction:</bold> Sarcoidosis is a challenging multisystemic inflammatory disease uncovering many clinical phenotypes. Clinicians are in need of diagnostic and prognostic robust biomarkers. Our study aims to characterize micro-RNA (miRNA) content of circulating serum exosomes in patients suffering from pulmonary sarcoidosis. <bold>Materials and Methods:</bold> We recruited 15 patients from ambulatory care at Liège University Hospital, sex- and age-matched with 15 healthy subjects. Exosomes were isolated from serum and miRNA was extracted and characterized. <bold>Results:</bold> We identified 58 altered exosomal miRNAs in sarcoidosis patients (fold change > 1.5, adjusted p-value < 0.1), of which 34 were upregulated and 24 were downregulated. Pathways analysis of predictive targets demonstrated an involvement of sarcoidosis-specific miRNAs in inflammatory disorders and fibrotic processes. Some miRNAs displayed correlation with lung function (FVC or DLCO) or with biological biomarkers (ACE or KL6). We investigated differential expression of sarcoidosis exosomal miRNA between stage 4 patients versus stage 2 patients and identified 14 altered miRNAs. <bold>Conclusion:</bold> Our preliminary study demonstrates that differentially expressed serum-derived exosomal miRNAs could be used as potential biomarkers in pulmonary sarcoidosis. In the future, we will apply our findings to a validation cohort and implement an integrated model with potential diagnostic and prognostic value.