TY - JOUR
T1 - Differential expression of sputum and serum autoantibodies in patients with chronic obstructive pulmonary disease
AU - Cass, Steven P.
AU - Dvorkin-Gheva, Anna
AU - Yang, Yuqiong
AU - McGrath, Joshua J.C.
AU - Thayaparan, Danya
AU - Xiao, Jing
AU - Wang, Fengyan
AU - Mukherjee, Manali
AU - Long, Fei
AU - Peng, Tao
AU - Nair, Parameswaran
AU - Liang, Zhenyu
AU - Stevenson, Christopher S.
AU - Li, Quan Zhen
AU - Chen, Rongchang
AU - Stampfli, Martin R.
N1 - Funding Information:
This study was supported by the Canadian Institutes of Health Research Grant PJT-159792, RespiVert, Ltd., part of Janssen Pharmaceuticals, National Key R&D Program of China Grant 2017YFC1310600, Guangzhou Healthcare Collaborative Innovation Major Project Grant 201604020012, and Medical Scientific Research Foundation of Guangdong Province Grant C2017050.
Funding Information:
M. Mukherjee reports grants from Canadian Institutes of Health Research, grants from Canadian Allergy, Asthma, and Immunology Foundation, grants from Methapharm Specialty Pharmaceuticals, personal fees from AstraZeneca, outside the submitted work; P. Nair reports grants and personal fees from AZ, grants from Novartis, grants and personal fees from Teva, grants from Sanofi, grants and personal fees from Roche, personal fees from Novartis, personal fees from Merck, personal fees from Equillium, personal fees from GSK, outside the submitted work; C. S. Stevenson reports employment at Johnson and Johnson outside the submitted work; M. R. Stampfli reports grants from Canadian Institutes of Health Research, grants from RespiVert Ltd. part of Janssen Pharmaceuticals, during the conduct of the study. None of the other authors has any conflicts of interest, financial or otherwise, to disclose.
Publisher Copyright:
Copyright © 2021 the American Physiological Society
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
KW - Autoantibody
KW - Autoimmune
KW - COPD
KW - Serum
KW - Sputum
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UR - http://www.scopus.com/inward/citedby.url?scp=85108741953&partnerID=8YFLogxK
U2 - 10.1152/AJPLUNG.00518.2020
DO - 10.1152/AJPLUNG.00518.2020
M3 - Article
C2 - 33908260
AN - SCOPUS:85108741953
SN - 0363-6135
VL - 320
SP - L1169-L1182
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 6
ER -