Reduced sputum expression of interferon-stimulated genes in severe COPD

Clarissa Hilzendeger,1 Jane da Silva,2 Monique Henket,1 Florence Schleich,1 Jean Louis Corhay,1 Tatiana Kebadze,3 Michael R Edwards,3 Patrick Mallia,3 Sebastian L Johnston,3 Renaud Louis1 1Department of Respiratory Medicine, Centre Hospitalier Universitaire (CHU) Liege, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA) I3 University of Liege, Belgium; 2Department of Medicine, Post-graduate Program in Health Sciences, University of Southern Santa Catarina, Palhoça-SC, Brazil; 3Airway Disease Division, Airway Disease Infection Section, National Heart and Lung Institute, Imperial College, London, UK Background: Exacerbations of COPD are frequent and commonly triggered by respiratory tract infections. The purpose of our study was to investigate innate immunity in stable COPD patients.Methods: Induced sputum was collected from 51 stable consecutive COPD patients recruited from the COPD Clinic of CHU Liege and 35 healthy subjects. Expression of interferons beta (IFN-β) and lambda1 (IL-29), IFN-stimulated genes (ISGs) MxA, OAS, and viperin were measured in total sputum cells by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The presence of Picornaviruses was assessed by RT-PCR, while potential pathogenic microorganisms (PPM) were identified by sputum bacteriology.Results: Expression of IL-29 was found in 16 of 51 COPD patients (31%) and in nine of 35 healthy subjects (26%), while IFN-β was detected in six of 51 COPD patients (12%) and in two of 35 healthy subjects (6%). ISGs were easily detectable in both groups. In the whole group of COPD patients, OAS expression was decreased (P<0.05), while that of viperin was increased (P<0.01) compared to healthy subjects. No difference was found with respect to MxA. COPD patients from group D of Global Initiative for Chronic Obstructive Lung Disease (GOLD) had reduced expression of all three ISGs (P<0.01 for MxA, P<0.05 for OAS, and P<0.01 for viperin) as compared to those of group B patients. Picornaviruses were detected in eight of 51 (16%) COPD patients vs four of 33 (12%) healthy subjects, while PPM were detected in seven of 39 (18%) COPD patients and associated with raised sputum neutrophil counts. IFN-β expression was raised when either picornavirus or PPM were detected (P=0.06), but no difference was seen regarding IL-29 or ISGs.Conclusion: ISGs expression was reduced in severe COPD that may favor exacerbation and contribute to disease progress by altering response to infection. Keywords: COPD, innate immunity, interferon-β, interferon-λ1, interferon-stimulated genes