title: Secretory IgA from submucosal glands does not compensate for its airway surface deficiency in chronic obstructive pulmonary disease.
abstract: 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) fluid 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 that MUC5AC is the predominant mucin expressed by airway epithelial cells, whereas MUC5B is expressed in submucosal glands of large airways. Dual immunostaining with anti-IgA and anti-MUC5B antibodies showed reduction of IgA on the airway surface as well as accumulation of IgA within MUC5B-positive luminal mucus plugs, suggesting that luminal SIgA originates from submucosal glands in COPD patients. We found that the concentration of SIgA in BAL is inversely correlated with forced expiratory volume in 1 s (FEV1) in COPD, but that the ratio of SIgA/MUC5B is 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.
authors.affiliation: Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, School of Medicine, Vanderbilt University, Nashville, TN, 37232-2650, USA.
authors.forename: Rui-Hong
authors.initials: RH
authors.lastname: Du
authors.affiliation: Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, School of Medicine, Vanderbilt University, Nashville, TN, 37232-2650, USA.
authors.forename: Bradley W
authors.initials: BW
authors.lastname: Richmond
authors.affiliation: Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, School of Medicine, Vanderbilt University, Nashville, TN, 37232-2650, USA.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Blackwell
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Cates
authors.affiliation: Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, School of Medicine, Vanderbilt University, Nashville, TN, 37232-2650, USA.|Department of Cancer Biology, School of Medicine, Vanderbilt University, Nashville, TN, USA.|Department of Veterans Affairs Medical Center, School of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Pierre P
authors.initials: PP
authors.lastname: Massion
authors.affiliation: Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, School of Medicine, Vanderbilt University, Nashville, TN, 37232-2650, USA.|Department of Pathology, Microbiology and Immunology, School of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Lorraine B
authors.initials: LB
authors.lastname: Ware
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, USA.
authors.forename: Jae Woo
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Pathology, Omsk State Medical Academy, Omsk, Russia.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Kononov
authors.affiliation: Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, School of Medicine, Vanderbilt University, Nashville, TN, 37232-2650, USA.|Department of Veterans Affairs Medical Center, School of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Lawson
authors.affiliation: Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, School of Medicine, Vanderbilt University, Nashville, TN, 37232-2650, USA.|Department of Cell and Developmental Biology, School of Medicine, Vanderbilt University, Nashville, TN, USA.|Department of Cancer Biology, School of Medicine, Vanderbilt University, Nashville, TN, USA.|Department of Veterans Affairs Medical Center, School of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Blackwell
authors.affiliation: Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, School of Medicine, Vanderbilt University, Nashville, TN, 37232-2650, USA. vasiliy.v.polosukhin@vanderbilt.edu.
authors.forename: Vasiliy V
authors.initials: VV
authors.lastname: Polosukhin
keywords: Chronic obstructive pulmonary disease; MUC5AC; MUC5B; Secretory IgA; Submucosal glands