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Increased circulating ?₂-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. ?₂-adrenergic receptors (?₂-ARs) are important targets in COPD therapy. ?₂-adrenergic receptor autoantibodies (?₂-AAbs), which may directly affect ?₂-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 ?₂-AR second extracellular loop peptides) rat models, we found that CS-exposed rats showed higher serum ?₂-AAb levels than control rats before alveolar airspaces became enlarged. Active-immune rats showed increased serum ?₂-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 ?₂-AAb levels were positively correlated with the RV/TLC (residual volume/total lung capacity) ratio (r?=?0.455, p?2-AAb levels exhibited worse alveolar airspace destruction. We suggest that increased circulating ?₂-AAbs are associated with smoking-related emphysema.

SUBMITTER: Hu JY

PROVIDER: S-EPMC5338268 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Increased circulating β2-adrenergic receptor autoantibodies are associated with smoking-related emphysema.

Hu Jia-Yi JY Liu Bei-Bei BB Du Yi-Peng YP Zhang Yuan Y Zhang Yi-Wei YW Zhang You-Yi YY Xu Ming M He Bei B

Scientific reports 20170306

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 increa ...[more]

PMID: 28262783

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Project description:BackgroundAmong various cardiac autoantibodies (AAbs), those recognizing the β1-adrenergic receptor (β1AR) demonstrate agonist-like effects and induce myocardial damage that can be reversed by β-blockers and immunoglobulin G3 (IgG3) immunoadsorption.ObjectivesThe goal of this study was to investigate the role of β1AR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy.MethodsPeripheral blood samples were drawn at enrollment in patients with recent-onset cardiomyopathy (left ventricular ejection fraction [LVEF] ≤0.40; <6 months). The presence of IgG and IgG3-β1AR-AAb was determined, and echocardiograms were assessed, at baseline and 6 months. Patients were followed up for ≤48 months.ResultsAmong the 353 patients who had blood samples adequate for the analysis, 62 (18%) were positive for IgG3-β1AR-AAbs (IgG3 group), 58 (16%) were positive for IgG but not IgG3 (non-IgG3 group), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. Left ventricular end-diastolic and end-systolic diameters were significantly larger in the non-IgG3 group compared with the other groups (left ventricular end-diastolic diameter, p < 0.01; left ventricular end-systolic diameter, p = 0.03). At 6 months, LVEF was significantly higher in the IgG3 group (p = 0.007). Multiple regression analysis showed that IgG3-β1AR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, β = 0.20, p = 0.01; change in LVEF, β = 0.20, p = 0.008). In patients with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had a lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint.ConclusionsIgG3-β1AR-AAbs were associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy.

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Increased circulating ?₂-adrenergic receptor autoantibodies are associated with smoking-related emphysema.

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Increased circulating β<sub>2</sub>-adrenergic receptor autoantibodies are associated with smoking-related emphysema.

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Increased circulating ?2-adrenergic receptor autoantibodies are associated with smoking-related emphysema.

Publications

Increased circulating β<sub>2</sub>-adrenergic receptor autoantibodies are associated with smoking-related emphysema.

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OmicsDI is part of the ELIXIR infrastructure

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Increased circulating ?₂-adrenergic receptor autoantibodies are associated with smoking-related emphysema.