Differential expression of sputum and serum autoantibodies in patients with chronic obstructive pulmonary disease

Author:

Cass Steven P.1,Dvorkin-Gheva Anna2,Yang Yuqiong3,McGrath Joshua J.C.1,Thayaparan Danya1,Xiao Jing4,Wang Fengyan4,Mukherjee Manali5ORCID,Long Fei4,Peng Tao4,Nair Parameswaran5,Liang Zhenyu3,Stevenson Christopher S.6,Li Quan-Zhen7,Chen Rongchang38,Stampfli Martin R.235ORCID

Affiliation:

1. Medical Sciences Graduate Program, McMaster University, Hamilton, Ontario, Canada

2. Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada

3. 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, Guangdong, People’s Republic of China

4. State Key Laboratory of Respiratory Disease, Sino-French Hoffmann Institute, College of Basic Medical Science, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China

5. Department of Medicine, Firestone Institute of Respiratory Health at St. Joseph’s Health Care, McMaster University, Hamilton, Ontario, Canada

6. Janssen Disease Interception Accelerator, Janssen Pharmaceutical Companies of Johnson and Johnson, Raritan, New Jersey

7. Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas

8. Shenzhen Institute of Respiratory Diseases, Shenzhen People’s Hospital, Shenzhen, Guangdong, People’s Republic of China

Abstract

Chronic obstructive pulmonary disease (COPD) is a complex and progressive respiratory disease. Autoimmune processes have been hypothesized to contribute to disease progression; however, the presence of autoantibodies in the serum has been variable. Given that COPD is a lung disease, we sought to investigate whether autoantibodies in sputum supernatant would better define pulmonary autoimmune processes. Matched sputum and serum samples were obtained from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study and at the Guangzhou Institute of Respiratory Health (GIRH). Samples were collected from patients with varying severity of COPD, asymptomatic smokers, and healthy control subjects. IgG and IgM autoantibodies were detected in sputum and serum of all subjects in both cohorts using a broad-spectrum autoantigen array. No differences were observed in sputum autoantibodies between COPD and asymptomatic smokers in either cohort. In contrast, 16% of detectable sputum IgG autoantibodies were decreased in subjects with COPD compared to healthy controls in the ADEPT cohort. Compared to asymptomatic smokers, approximately 13% of detectable serum IgG and 40% of detectable serum IgM autoantibodies were differentially expressed in GIRH COPD subjects. Of the differentially expressed specificities, anti-nuclear autoantibodies were predominately decreased. A weak correlation between increased serum IgM anti-tissue autoantibodies and a measure of airspace enlargement was observed. The differential expression of specificities varied between the cohorts. In closing, using a comprehensive autoantibody array, we demonstrate that autoantibodies are present in subjects with COPD, asymptomatic smokers, and healthy controls. Cohorts displayed high levels of heterogeneity, precluding the utilization of autoantibodies for diagnostic purposes.

Funder

RespiVert Ltd, Part of Janssen Pharamaceuticals

National Key R&D Program of China

Guangzhou Healthcare Collaborative Innovation Major Project

Medical Foundation of Guangdong Province

Gouvernement du Canada | Canadian Institutes of Health Research

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology

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