摘要：

Secretory immunoglobulin A (SIgA) reaches the airway lumen by local transcytosis across airway epithelial cells or with tracheobronchial submucosal gland secretions. In chronic obstructive pulmonary disease (COPD), deficiency of SIgA on the airway surface has been reported, however, reduction of SIgA levels in sputum and bronchoalveolar lavage (BAL) has not been consistently observed. To explain this discrepancy, we analyzed BAL fluid and lung tissue from patients with COPD and control subjects. Immunohistochemical analysis of large and small airways of COPD patients showed MUC5AC was the predominant mucin expressed by airway epithelial cells, whereas MUC5B was expressed in submucosal glands of large airways. In addition to showing a reduction of IgA on the airway surface, dual immunostaining with anti-IgA and anti-MUC5B antibodies showed an accumulation of IgA within MUC5B-positive luminal mucus plugs, suggesting that luminal SIgA originates from submucosal glands in COPD patients. Although the concentration of SIgA in BAL inversely correlated with FEV1 in COPD, the ratio of SIgA/MUC5B was a better predictor of FEV1, particularly in patients with moderate COPD. Together, these findings suggest that SIgA production by submucosal glands, which are expanded in COPD, is insufficient to compensate for reduced SIgA transcytosis by airway epithelial cells. Localized SIgA deficiency on the surface of small airways is associated with COPD progression and represents a potential new therapeutic target in COPD.

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