Abstract
BACKGROUND: Autoimmunity plays a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the autoantibody responses and their clinical correlation patterns in COPD patients with and without airway eosinophilic inflammation are unknown. The aim of this study was to compare the autoantibody profiles and their clinical associations in stable COPD patients, stratified by airway inflammatory phenotypes. METHODS: Matched sputum and serum, obtained from 62 stable COPD patients and 14 age-matched controls, were assayed for the presence of IgG and IgM antibodies against 13 autoantigens using protein array. A sputum eosinophil count ≥3% was used as cut-off value to stratify COPD patients into eosinophilic and non-eosinophilic groups. Correlation network analysis was used to evaluate the correlation patterns among autoantibody and clinical variables in each group. RESULTS: There were no significant differences of clinical parameters and autoantibody levels between the two COPD groups. In non-eosinophilic COPD, sputum anti-CytochromeC_IgG and anti-Aggrecan_IgM were significantly higher than those in healthy controls, and prior exacerbation was positively associated with lung function and sputum anti-Collagen-IV_IgG. While in eosinophilic COPD, sputum/serum anti-heat shock protein (HSP)47_IgG, serum anti-HSP70_IgG and serum anti-Amyloid-beta_IgG were significantly lower than those in healthy controls, and no significant correlation between prior exacerbations and lung function was found. Differences were also observed in network hubs, with the network for non-eosinophilic COPD possessing 9 hubs comprising two lung function parameters and seven autoantibodies, compared with eosinophilic COPD possessing 12 hubs all comprising autoantibodies. CONCLUSIONS: Autoantibody responses were heterogeneous and differentially correlated with the exacerbation risk and other clinical parameters in COPD patients of different inflammatory phenotypes. These findings provide useful insight into the need for personalized management for preventing COPD exacerbations.