Changes in Blood Immune Cell Transcriptomes Associate With Disease Severity, Infection, and Inflammation in Bronchiectasis Patients: Data From the EMBARC-BRIDGE Study
Rationale:
Bronchiectasis is a chronic inflammatory disease, but the mechanisms underlying disease severity are poorly understood.
We performed the largest transcriptomics study inbronchiectasis to-date to investigate associations between immune cell gene expression,inflammation, infection and clinical characteristics.
Methods:
RNA-stabilised peripheral bloodsamples from people with stable bronchiectasis participating in an international, multi-centreobservational study (BRIDGE; NCT03791086) and from matched healthy controls were analysed.
Results:
Comparison of peripheral blood immune cell transcriptomes between people with bronchiectasis and matched controls yielded 5561 significant differentially expressed genes.
Gene set enrichment analysis and pathway clustering analysis showed that 18 of the top 25 differential pathways identified were related to cell metabolism, including oxidative phosphorylationand electron transport chain, all of which were suppressed in bronchiectasis.
218 DEGs were identified between those with mild-to-moderate and severe disease.
The top 25 differential pathways clustered primarily into two sets, one relating to innate immune responses including defence against bacteriaand viruses, which were enriched, and the other to RNA processing including mitochondrial translation, which were suppressed.
Imputation of immune cell proportions showed significantly lower proportions of naive B cells in severe bronchiectasis and higher neutrophil proportions.
There were 222 DEGs between patients ever having recorded Pseudomonas aeruginosa positivity on sputum culture and those without. In patients with and without long term azithromycin use where significant pathways included suppression of B cell signalling and increase in those related to TNF regulation.
Conclusions:
Marked differences in peripheral blood immune cellgene expression were observed between bronchiectasis patients and healthy controls.Transcriptomic changes were associated with disease severity and airway inflammation identifyingpotential novel biomarkers and therapeutic targets
Authors:
M. B. Long, L. Perea M. K. Shuttleworth, J. Pollock, C. Hughes, C. Clarke, M. Shteinberg, S.Aliberti, C. Haworth, S. H. Chotirmall, E. Polverino, P. C. Goeminne, M. R. Loebinger, N.Lorent, F. Ringshausen, R. Faner, O. Sibila, A. Shoemark, J. D. Chalmers.
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Those interested in the specific molecular mechanisms, the methods used, and the detailed analyses of the pathways involved can refer to the original article for a deeper understanding of these findings and their clinical implications.
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