C106-15 Transcriptomic Features of Peripheral Blood Mononuclear Cells in Patients With a History of Mycobacterium Avium Complex Pulmonary Disease

Rationale Mycobacterium avium complex pulmonary disease (MAC-PD) can be caused by various factors, including environmental exposure to MAC, underlying pulmonary diseases, and host immunosuppression. Peripheral blood mononuclear cells (PBMCs), such as monocytes and lymphocytes, play a central role in the immune response to MAC infection. However, the relationship between the pathogenesis of MAC-PD and the transcriptomic features of PBMCs remains unclear. Methods PBMCs were collected from five patients with a history of MAC-PD and from five healthy controls. The PBMC transcriptome was analyzed using bulk RNA sequencing. The inclusion criteria were as follows: confirmed diagnosis of MAC-PD, achievement of negative sputum cultures after antibiotic therapy, and maintenance of negative cultures for more than two months following treatment completion. Furthermore, single-cell RNA sequencing of PBMCs was conducted for three of the patients. Results Principal component analysis clearly distinguished the MAC-PD group from healthy controls, identifying 84 differentially expressed genes (DEGs), including IL18, LPAR1, and IL17RC. Enrichment analysis revealed upregulation of immune-related pathways such as natural killer (NK) and natural killer T (NKT) cell proliferation, IL17A signaling, and helper T-cell responses, as well as downregulation of metal ion transport pathways in PBMC from patients with a history of MAC-PD. In addition, cell subpopulations expressing these DEGs were identified, and the differentiation states of immune cell subsets were evaluated by single-cell RNA sequence. Conclusions The transcriptomic features of PBMCs may reflect and contribute to the pathogenesis of MAC-PD.