Dissociation between airway and systemic autoantibody responses in chronic obstructive pulmonary disease

Zhenyu Liang; Fei Long; Kuimiao Deng; Fengyan Wang; Jing Xiao; Yuqiong Yang; Dongying Zhang; Weili Gu; Jiaxuan Xu; Wenhua Jian; Weijuan Shi; Jinping Zheng; Xin Chen; Yang Gao; Qun Luo; Martin R Stampfli; Tao Peng; Rongchang Chen

doi:10.21037/atm-20-944

Dissociation between airway and systemic autoantibody responses in chronic obstructive pulmonary disease

Ann Transl Med. 2020 Aug;8(15):918. doi: 10.21037/atm-20-944.

Authors

Zhenyu Liang¹, Fei Long², Kuimiao Deng¹, Fengyan Wang¹, Jing Xiao², Yuqiong Yang¹, Dongying Zhang¹, Weili Gu¹, Jiaxuan Xu¹, Wenhua Jian¹, Weijuan Shi¹, Jinping Zheng¹, Xin Chen³, Yang Gao¹, Qun Luo¹, Martin R Stampfli⁴, Tao Peng², Rongchang Chen^{1

5}

Affiliations

¹ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
² State Key Laboratory of Respiratory Disease, Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China.
³ Department of Respiratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
⁴ Department of Medicine, Firestone Institute of Respiratory Health at St. Joseph's Healthcare, McMaster University, Hamilton, ON, Canada.
⁵ Pulmonary and Critical Care Department, Shenzhen Institute of Respiratory Disease, Shenzhen People's Hospital, Shenzhen, China.

Abstract

Background: Autoimmune processes have been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the relationship between airway and systemic autoantibody responses remains unclear. The aim of this study was to elucidate this relationship in patients with stable COPD by investigating the correlation patterns between sputum and serum autoantibodies.

Methods: In this cross-sectional study, sputum supernatant and serum obtained from 47 patients with stable COPD were assayed for the presence of IgG antibodies against ten autoantigens: Smith antigen (Sm), ribosomal phosphoprotein P0 (P0), Ro/Sjögren syndrome type A antigen (Ro/SSA), La/Sjögren syndrome type B antigen (La/SSB), DNA topoisomerase I (Scl-70), histidyl-tRNA synthetase (Jo-1), U1 small nuclear ribonucleoprotein (U1-SnRNP), thyroid peroxidase (TPO), proteinase-3 (PR3), and myeloperoxidase (MPO). A second cohort of 55 stable COPD patients was recruited for validation, and a group of 59 non-COPD controls and a group of 20 connective-tissue disease-associated interstitial lung disease (CTD-ILD) patients were also recruited for comparison. Hierarchical clustering and network analysis were used to evaluate the correlation patterns between sputum and serum autoantibody profiles.

Results: Both hierarchical clustering and network analysis showed that sputum and serum autoantibody profiles were distinct in either analytic COPD cohort or validation cohort. In contrast, the autoantibodies of the two compartments in non-COPD controls and CTD-ILD patients were inadequately distinguished using either hierarchical clustering or network analysis. Many autoantibodies in the sputum were found to have significant correlations with lung function, symptom score and frequency of prior exacerbations in COPD patients, but the antibodies in the serum were not.

Conclusions: We observed a dissociation between sputum autoantibodies and serum autoantibodies in patients with stable COPD, suggesting that airway and systemic immune status may play very different roles in the disease. Sputum autoantibodies are more clinically relevant than serum autoantibodies. Focusing on airway autoimmunity may help improve understanding of the immunopathological mechanism of COPD.

Keywords: Chronic obstructive pulmonary disease (COPD); autoantibody; autoimmunity; correlation pattern; network analysis; unbiased classification.