Characterising interferon responses in bronchiectasis patients in the EMBARC-BRIDGE study

<bold>Intro:</bold> Interferon (IFN) signalling is induced in response to infections and is crucial to limit viral replication. Whilst viral infections have a significant impact in bronchiectasis, IFN signalling in these patients is not well investigated. We aimed to investigate basal levels of IFN signalling in stable bronchiectasis patients. <bold>Methods:</bold> mRNA sequencing was performed in whole blood from clinically-stable bronchiectasis patients enrolled in an international, observational study (EMBARC-BRIDGE study). Multiplex immunoassays were used to measure sputum IFN-y, and also serum CXCL10 and IFN-y in a participant subset. <bold>Results:</bold> 163 patients were included, mean age was 65.1±15.5 and 46.6% were female. Participants with the highest levels of sputum or serum IFN-y or IFN-inducible CXCL10 (upper quartile; >0.34415, >8.105, >146.86 pg/ml, respectively) were compared to those with lower levels. 202 differentially-expressed genes (DEGs; adjusted-pvalue<0.05) were identified in patients with the highest CXCL10 levels, including IFN-induced genes IFI44L, RSAD2 and IFI44 which were significantly upregulated. IFI44L and RSAD2 were also amongst those significantly upregulated of the 523 DEGs in the high serum IFN-y group. In patients with the highest levels of sputum IFN-y, we identified 21 DEGs, though none of these were clearly linked to interferon signalling. <bold>Conclusion:</bold> Interferon signalling is observed in stable bronchiectasis patients and significant upregulation of interferon-inducible genes was seen in those with high serum IFN levels. However, higher airway IFN-y levels were not associated with systemic changes in interferon-signalling genes suggesting local mucosal interferon responses.