Antimicrobial Peptides SLPI and Beta Defensin-1 in Sputum are Negatively Correlated with FEV1

Abstract

Jennifer Cane,1,2 Laura Tregidgo,1 Samantha Thulborn,1,2 Donna Finch,3 Mona Bafadhel1,2 1Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK; 2Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK; 3Alchemab Therapeutics, Cambridge, UKCorrespondence: Jennifer Cane Email [email protected]: Chronic obstructive pulmonary disease (COPD) and asthma have heterogeneous inflammation with inhaled corticosteroids (ICS) as a mainstay of treatment. There is increased prevalence of non-typeable Haemophilus influenzae (NTHi) persistence in airways of patients with neutrophilic airway inflammation, potentially due to suppressed host defence after corticosteroid treatment. Antimicrobial peptides (AMPs) have antimicrobial activity against pathogens and immunomodulatory effects. We investigated whether AMPs associate with NTHi presence in COPD and asthma, and whether ICS alter this.Methods: Secretory leukocyte protease inhibitor (SLPI), osteopontin, elafin and beta defensin-1 were measured in sputum supernatants from healthy donors (n=9), asthmatics (n=21) and patients with COPD (n=14). Elafin and beta defensin-1 were measured in a primary human bronchial epithelial cells (HBECs) from healthy and COPD donors infected with NTHi and pre-treated with fluticasone propionate (FP) and budesonide (BUD). Internalised NTHi was quantified by qPCR.Results: Sputum SLPI was negatively correlated with FEV1 (p< 0.001, r=− 0.610), FEV1% predicted (p< 0.001, r=− 0.583) and FEV1/FVC (p=0.001, r=− 0.528). Sputum beta defensin-1 was negatively associated with FEV1 (p< 0.001***r=− 0.594). SLPI and beta defensin-1 levels in sputum were higher in the healthy controls and COPD group compared to the asthma group (p=0.001 and p=0.014) and (p< 0.001 and p=0.007, respectively). ICS use was associated with higher sputum osteopontin compared to those with no ICS use. NTHi infection of COPD HBECs produced higher levels of beta defensin-1 compared to healthy donors (mean (SD) release: 45.1pg/mL (7.3) vs 21.2pg/mL (7.3) respectively, p=0.014). Elafin release from HBECs from COPD donors did not change following NTHi infection; however, elafin from healthy donors was significantly reduced (%mean reduction: 23.7%, 95% confidence intervals (CI) of reduction: 5.3– 38.4%, p< 0.01).Conclusion: Sputum SLPI and beta defensin-1 may be markers to identify those patients with declining lung function. ICS use was associated with higher sputum osteopontin compared to those with no ICS use.Keywords: antimicrobial peptide, non-typeable haemophilus influenzae, chronic obstructive pulmonary disease

Keywords

• antimicrobial peptide
• non-typeable haemophilus influenzae
• chronic obstructive pulmonary disease