title: Increased expression of A Proliferation-inducing Ligand (APRIL) in lung leukocytes and alveolar epithelial cells in COPD patients with non small cell lung cancer: a possible link between COPD and lung cancer?
abstract: BACKGROUND
  Chronic Obstructive Pulmonary Disease (COPD) is characterized by an excessive activation of the adaptive immune system and, in particular, uncontrolled expansion of the B-cell pool. One of the key promoters of B cell expansion is A PRoliferation-Inducing Ligand (APRIL). APRIL has been strongly linked to non small cell lung cancer (NSCLC) onset and progression previously. However, little is known about the expression of APRIL in the lungs of COPD patients.
  
  
  METHODS
  Using immuno-fluorescence staining, the expression of APRIL was assessed in sections of lungs from 4 subjects with primary diagnosis of COPD (FEV1 33 ± 20 % predicted), 4 subjects with primary diagnosis of NSCLC, 4 subjects diagnosed with both COPD and NSCLC, smokers without COPD or NSCLC and 3 healthy never-smokers. The percentage of B cells, alveolar macrophages (AMs) and polymorphonuclear neutrophils (PMNs) in the lung and alveolar epithelial cells (AECs) that stained positively for APRIL was quantified using epi-fluorescence microscopy and image analysis software.
  
  
  RESULTS
  The percentage of APRIL-expressing B cells, AMs, PMNs and alveolar epithelial cells (AECs) was higher in patients having both COPD and NSCLC than in patients with either COPD or NSCLC alone, SC or NSC (p < 0.03 for all comparisons). The percentage of APRIL-expressing AMs and AECs (but not in B cells) was higher in patients with NSCLC alone than in patients with COPD alone. The percentage of APRIL-expressing AECs (but not B cells or AMs) was higher in COPD patients than in SC and NSC (p < 0.05 for all comparisons). The percentage of APRIL-expressing B cells, AMs and AECs cells was similar in NSC and SC.
  
  
  CONCLUSIONS
  The percentage of APRIL-expressing B cells, AMs and AECs is higher in the lungs of patients with both COPD and NSCLC than in patients with COPD or NSCLC alone or control subjects. These findings suggest that APRIL may contribute to the pathogenesis of both COPD and NSCLC, and possibly to the development of NSCLC in patients with established COPD.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Room 855B, Harvard Institutes of Medicine Building, 77 Avenue Louis Pasteur, Boston, MA 02115 USA.|Lovelace Respiratory Research Institute, Albuquerque, NM USA.|University of Parma, Parma, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Polverino
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Room 855B, Harvard Institutes of Medicine Building, 77 Avenue Louis Pasteur, Boston, MA 02115 USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Laucho-Contreras
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Room 855B, Harvard Institutes of Medicine Building, 77 Avenue Louis Pasteur, Boston, MA 02115 USA.
authors.forename: Joselyn
authors.initials: J
authors.lastname: Rojas Quintero
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Room 855B, Harvard Institutes of Medicine Building, 77 Avenue Louis Pasteur, Boston, MA 02115 USA.|Lovelace Respiratory Research Institute, Albuquerque, NM USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Divo
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Room 855B, Harvard Institutes of Medicine Building, 77 Avenue Louis Pasteur, Boston, MA 02115 USA.|Lovelace Respiratory Research Institute, Albuquerque, NM USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Pinto-Plata
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA USA.
authors.forename: Lynette
authors.initials: L
authors.lastname: Sholl
authors.affiliation: Clinica Universidad de Navarra, Pamplona, Spain.
authors.forename: Juan P
authors.initials: JP
authors.lastname: de-Torres
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Room 855B, Harvard Institutes of Medicine Building, 77 Avenue Louis Pasteur, Boston, MA 02115 USA.|Lovelace Respiratory Research Institute, Albuquerque, NM USA.
authors.forename: Bartolome R
authors.initials: BR
authors.lastname: Celli
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Room 855B, Harvard Institutes of Medicine Building, 77 Avenue Louis Pasteur, Boston, MA 02115 USA.|Lovelace Respiratory Research Institute, Albuquerque, NM USA.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Owen
keywords: APRIL; Adaptive immunity; Autoimmunity; COPD; Innate immunity; Non small cell lung cancer