OR23
Single-cell RNA sequencing shows that circulating monocytes enriched in IFN signaling are associated with nontuberculous mycobacteria pulmonary disease in cystic fibrosis
N I Lorè(1) S de Pretis(1) A Gramegna(2) F Nicola(1) F Di Marco(1) S Saldarini(1) C Contarini(2) C Ferrari(1) S Saliu(1) L Cariani(2) F Blasi(2) D Cirillo(1)
1:San Raffael Scientific Institute; 2:Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
Background: People colonized with Mycobacterium abscessus, such as people with cystic fibrosis (PwCF) or chronic respiratory diseases, are at risk of nontuberculous mycobacterial pulmonary disease (NTM-PD) and have heterogeneous clinical outcomes. New reliable biomarkers, such as immune signatures, are among the unmet needs for better clinical management of NTM-PD.
Methods: We collected blood samples from PwCF with no history of NTM detection and clinically stable (CF), with NTM-positive isolates and clinically stable (CF-NTM), and with NTM-positive isolates and a clinical diagnosis for risk of pulmonary disease (CF-NTM-PD). We isolated peripheral blood mononuclear cells (PBMCs) and plasma to perform scRNA-sequencing and Luminex assay.
Results: We performed scRNAseq on PBMCs samples, identifying 10 cellular immune populations according to expression levels of canonical markers. We performed differentially expressed gene (DEG) analysis in the three groups in each cell population to identify transcriptomic signatures characterizing CF-NTM-PD. We compared DEGs in samples from people at risk of pulmonary disease (CF-NTM-PD) with those from the other two groups (CF, CF-NTM) and identified unique RNA transcriptomic profiles activated in monocytes that were specifically upregulated in the CD14+ monocyte cluster of CF-NTM-PD. The unique RNA transcriptomic profiles in CD14+ cells were further validated using a second public bulk RNA dataset from a cohort of individuals with pwCF and NTM-PD.
Conclusions: Our scRNA-sequencing data suggest that monocyte responses are present in PwCF at risk of NTM-PD.
Acknowledgements: This work was supported by FFC#7/2022 and FFC#20/2020 from the Fondazione Italiana per la ricerca sulla Fibrosi Cistica.