International Journal of COPD (Jan 2020)
Serum Levels of Autoantibodies Against Extracellular Antigens and Neutrophil Granule Proteins Increase in Patients with COPD Compared to Non-COPD Smokers
Abstract
Aiping Ma,1,* Lifang Wen,2,* Junping Yin,3 Yi Hu,4 Xiaoyang Yue,3 Jiurong Li,1 Xiaoru Dong,2 Yask Gupta,5 Ralf J Ludwig,5 Susanne Krauss-Etschmann,3,6 Gabriela Riemekasten,7 Frank Petersen,3 Xinhua Yu2,3 1Department of Respiratory Medicine, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 2Xiamen-Borstel Joint Laboratory of Autoimmunity, The Medical College of Xiamen University; 3Priority Area Asthma and Allergy, Research Center Borstel, Airway Research Center North (ARCN), Members of the German Center for Lung Research (DZL), Borstel, Germany; 4Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 5Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany; 6Institute for Experimental Medicine, Christian-Albrechts-Universitaetzu Kiel, Kiel, Germany; 7Department of Rheumatology, University of Lübeck, Lübeck 23538, Germany*These authors contributed equally to this workCorrespondence: Xinhua YuPriority Area Asthma and Allergy, Research Center Borstel, Borstel 23845, GermanyTel +49 453 7188 2520Email [email protected]: Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease leading to irreversible airflow limitation and is characterized by chronic pulmonary inflammation, obstructive bronchiolitis and emphysema. Etiologically, COPD is mediated by toxic gases and particles, eg, cigarette smoke, while the pathogenesis of the disease is largely unknown. Several lines of evidence indicate a link between COPD and autoimmunity but comprehensive studies are lacking.Methods: By using a protein microarray assaying more than 19,000 human proteins we determined in this study the autoantibody profiles of COPD and non-COPD smokers. The discovery cohort included 5 COPD patients under acute exacerbation (AECOPD) and 5 age- and gender-matched non-COPD smokers. One putative candidate autoantibody, anti-lactoferrin IgG, was further investigated by using immunoblotting with a large validation cohort containing 124 healthy controls, 92 patients with AECOPD and 52 patients with stable COPD.Results: We show that i) autoantigens targeted by autoantibodies with higher titers in COPD patients were enriched in extracellular regions, while those with lower titers in COPD patients were enriched in intracellular compartments. ii) levels of IgG autoantibodies against many neutrophil granule proteins were significantly higher in COPD patients than in non-COPD smokers. Furthermore, increased levels of anti-lactoferrin antibodies in COPD patients were confirmed in a cohort with a large number of samples.Conclusion: The comprehensive autoantibody profiles from COPD patients established in this study demonstrated for the first time a shift in the cellular localization of antigens targeted by autoantibodies in COPD.Keywords: chronic obstructive pulmonary disease, autoimmunity, autoantibody profile, neutrophil granule proteins, lactoferrin
