title: Increased circulating β2-adrenergic receptor autoantibodies are associated with smoking-related emphysema.
abstract: Smoking is a dominant risk factor for chronic obstructive pulmonary disease (COPD) and emphysema, but not every smoker develops emphysema. Immune responses in smokers vary. Some autoantibodies have been shown to contribute to the development of emphysema in smokers. β2-adrenergic receptors (β2-ARs) are important targets in COPD therapy. β2-adrenergic receptor autoantibodies (β2-AAbs), which may directly affect β2-ARs, were shown to be increased in rats with passive-smoking-induced emphysema in our current preliminary studies. Using cigarette-smoke exposure (CS-exposure) and active-immune (via injections of β2-AR second extracellular loop peptides) rat models, we found that CS-exposed rats showed higher serum β2-AAb levels than control rats before alveolar airspaces became enlarged. Active-immune rats showed increased serum β2-AAb levels, and exhibited alveolar airspace destruction. CS-exposed-active-immune treated rats showed more extensive alveolar airspace destruction than rats undergoing CS-exposure alone. In our current clinical studies, we showed that plasma β2-AAb levels were positively correlated with the RV/TLC (residual volume/total lung capacity) ratio (r = 0.455, p < 0.001) and RV%pred (residual volume/residual volume predicted percentage, r = 0.454, p < 0.001) in 50 smokers; smokers with higher plasma β2-AAb levels exhibited worse alveolar airspace destruction. We suggest that increased circulating β2-AAbs are associated with smoking-related emphysema.
authors.affiliation: Department of Respiratory Medicine, Peking University Third Hospital, Beijing, China.
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Hu
authors.affiliation: Department of Respiratory Medicine, Peking University Third Hospital, Beijing, China.
authors.forename: Bei-Bei
authors.initials: BB
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, Peking University Third Hospital, Beijing, China.
authors.forename: Yi-Peng
authors.initials: YP
authors.lastname: Du
authors.affiliation: Department of Respiratory Medicine, Peking University Third Hospital, Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Peking University Third Hospital, Beijing, China.
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health; Beijing Key Laboratory of cardiovascular Receptors Research, Beijing, China.
authors.forename: You-Yi
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health; Beijing Key Laboratory of cardiovascular Receptors Research, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Respiratory Medicine, Peking University Third Hospital, Beijing, China.
authors.forename: Bei
authors.initials: B
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D004195:Disease Models, Animal; D004646:Emphysema / Q000175:diagnosis* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D051381:Rats; D011941:Receptors, Adrenergic / Q000276:immunology*; D012907:Smoking / Q000009:adverse effects*
chemical_list: D001323:Autoantibodies; D011941:Receptors, Adrenergic