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

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.