Bronchial Secretory Immunoglobulin A Deficiency Correlates With Airway Inflammation and Progression of Chronic Obstructive Pulmonary Disease

摘要

Although airway inflammation can persist for years after smoking cessation in patients with chronic obstructive pulmonary disease (COPD), the mechanisms of persistent inflammation are largely unknown. Objectives: We investigated relationships between bronchial epithelial remodeling, polymeric immunoglobulin receptor (plgR) expression, secretory IgA (SlgA), airway inflammation, and mural remodeling in COPD. Methods: Lung tissue specimens and bronchoalveolar lavage were obtained from lifetime nonsmokers and former smokers with or without COPD. Epithelial structural changes were quantified by morphomet-ric analysis. Expression of plgR was determined by immunostaining and real-time polymerase chain reaction, immunohistochemistry was performed for IgA, CD4 and CD8 lymphocytes, and cytomegalovirus and Epstein-Barr virus antigens. Total IgA and SlgA were measured by ELISA and IgA transcytosis was studied using cultured human bronchial epithelial cells. Measurements and Main Results: Areas of bronchial mucosa covered by normal pseudostratified ciliated epithelium were characterized by plgR expression with SlgA present on the mucosal surface. In contrast, areas of bronchial epithelial remodeling had reduced plgR expression, localized SlgA deficiency, and increased CD4+ and CD8+ lymphocyte infiltration. In small airways (<2 mm), these changes were associated with presence of herpesvirus antigens, airway wall remodeling, and airflow limitation in patients with COPD. Patients with COPD had reduced SlgA in bronchoalveolar lavage. Air-liquid interface epithelial cell cultures revealed that complete epithelial differentiation was required for normal plgR expression and IgA transcytosis. Conclusions: Our findings indicate that epithelial structural abnormalities lead to localized SlgA deficiency in COPD airways. Impaired mucosal immunity may contribute to persistent airway inflammation and progressive airway remodeling in COPD. polymeric immunoglobulin receptor; bronchial epithelium; cell differentiation; epithelial remodeling; mucosal host defense