title: Bronchial secretory immunoglobulin a deficiency correlates with airway inflammation and progression of chronic obstructive pulmonary disease.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  We investigated relationships between bronchial epithelial remodeling, polymeric immunoglobulin receptor (pIgR) expression, secretory IgA (SIgA), 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 morphometric analysis. Expression of pIgR 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 SIgA were measured by ELISA and IgA transcytosis was studied using cultured human bronchial epithelial cells.
  
  
  RESULTS
  Areas of bronchial mucosa covered by normal pseudostratified ciliated epithelium were characterized by pIgR expression with SIgA present on the mucosal surface. In contrast, areas of bronchial epithelial remodeling had reduced pIgR expression, localized SIgA 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 SIgA in bronchoalveolar lavage. Air-liquid interface epithelial cell cultures revealed that complete epithelial differentiation was required for normal pIgR expression and IgA transcytosis.
  
  
  CONCLUSIONS
  Our findings indicate that epithelial structural abnormalities lead to localized SIgA deficiency in COPD airways. Impaired mucosal immunity may contribute to persistent airway inflammation and progressive airway remodeling in COPD.
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2650, USA. vasiliy.v.polosukhin@vanderbilt.edu
authors.forename: Vasiliy V
authors.initials: VV
authors.lastname: Polosukhin
authors.forename: Justin M
authors.initials: JM
authors.lastname: Cates
authors.forename: William E
authors.initials: WE
authors.lastname: Lawson
authors.forename: Rinat
authors.initials: R
authors.lastname: Zaynagetdinov
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Milstone
authors.forename: Pierre P
authors.initials: PP
authors.lastname: Massion
authors.forename: Sebahat
authors.initials: S
authors.lastname: Ocak
authors.forename: Lorraine B
authors.initials: LB
authors.lastname: Ware
authors.forename: Jae Woo
authors.initials: JW
authors.lastname: Lee
authors.forename: Russell P
authors.initials: RP
authors.lastname: Bowler
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Kononov
authors.forename: Scott H
authors.initials: SH
authors.lastname: Randell
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Blackwell
mesh_terms: D056151:Airway Remodeling / Q000276:immunology*; D001980:Bronchi / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D003587:Cytomegalovirus / Q000302:isolation & purification; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000032:analysis / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000503:physiopathology; D019056:Receptors, Polymeric Immunoglobulin / Q000276:immunology*; D012137:Respiratory System / Q000276:immunology; D012907:Smoking / Q000009:adverse effects* / Q000276:immunology; D013995:Time
chemical_list: D007071:Immunoglobulin A, Secretory; D019056:Receptors, Polymeric Immunoglobulin