Whole blood transcriptomics characterize molecular phenotypes of pulmonary Mycobacterium avium complex disease

Pulmonary Mycobacterium avium complex (MAC) disease shows a range of clinical phenotypes and responses to treatment. While Th1 immunity and neutrophils have been implicated in its pathogenesis, the precise mechanisms remain unclear. Furthermore, comprehensive gene expression analysis in this context are scarce. This study aimed to elucidate the heterogeneity of pulmonary MAC disease by gene expression profiling of whole blood cells. Unsupervised cluster analysis was performed on whole blood gene expression data at 0M. In addition, we also evaluated the variation in gene expression profiles of whole blood cells before (0M) and after starting treatment (1M) with guideline based therapy (GBT; azithromycin [AZM]/clarithromycin [CAM]+ethambutol [EB]+rifampicin [RFP]). Overall design: We enrolled 100 patients with pulmonary MAC disease requiring treatment according to standard guidelines. Whole blood cells were collected for RNA-sequencing before (0M) and one month (1M) after the start of guideline based therapy (GBT; azithromycin [AZM]/clarithromycin [CAM]+ ethambutol [EB]+rifampicin [RFP]). Unsupervised cluster analysis was performed on whole blood gene expression data at 0M. In addition, gene expressions in whole blood cells was compared between before (0M) and after starting treatment (1M) with GBT.