title: Network Analysis of Lung Transcriptomics Reveals a Distinct B-Cell Signature in Emphysema.
abstract: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation caused by a combination of airways disease (bronchiolitis) and parenchymal destruction (emphysema), whose relative proportion varies from patient to patient.
  
  
  
  To explore and contrast the molecular pathogenesis of emphysema and bronchiolitis in COPD.
  
  
  
  We used network analysis of lung transcriptomics (Affymetrix arrays) in 70 former smokers with COPD to compare differential expression and gene coexpression in bronchiolitis and emphysema.
  
  
  
  We observed that in emphysema (but not in bronchiolitis) (1) up-regulated genes were enriched in ontologies related to B-cell homing and activation; (2) the immune coexpression network had a central core of B cell-related genes; (3) B-cell recruitment and immunoglobulin transcription genes (CXCL13, CCL19, and POU2AF1) correlated with emphysema severity; (4) there were lymphoid follicles (CD20(+)IgM(+)) with active B cells (phosphorylated nuclear factor-κB p65(+)), proliferation markers (Ki-67(+)), and class-switched B cells (IgG(+)); and (5) both TNFRSF17 mRNA and B cell-activating factor protein were up-regulated. These findings were by and large reproduced in a group of patients with incipient emphysema and when patients with emphysema were matched for the severity of airflow limitation of those with bronchiolitis.
  
  
  
  Our study identifies enrichment in B cell-related genes in patients with COPD with emphysema that is absent in bronchiolitis. These observations contribute to a better understanding of COPD pathobiology and may open new therapeutic opportunities for patients with COPD.
authors.affiliation: 1 Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain.|2 Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Faner
authors.affiliation: 1 Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain.|2 Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Madrid, Spain.
authors.forename: Tamara
authors.initials: T
authors.lastname: Cruz
authors.affiliation: 3 Bioinformatics Platform Institut d'investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Casserras
authors.affiliation: 1 Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain.|2 Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Madrid, Spain.
authors.forename: Alejandra
authors.initials: A
authors.lastname: López-Giraldo
authors.affiliation: 2 Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Madrid, Spain.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Noell
authors.affiliation: 1 Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Coca
authors.affiliation: 4 GSK R&D, King of Prussia, Pennsylvania.
authors.forename: Ruth
authors.initials: R
authors.lastname: Tal-Singer
authors.affiliation: 4 GSK R&D, King of Prussia, Pennsylvania.
authors.forename: Bruce
authors.initials: B
authors.lastname: Miller
authors.affiliation: 1 Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain.|2 Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Madrid, Spain.|5 Respiratory Institute, Pulmonary Service, Hospital Clinic, Institut d'investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain; and.
authors.forename: Roberto
authors.initials: R
authors.lastname: Rodriguez-Roisin
authors.affiliation: 6 Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Avrum
authors.initials: A
authors.lastname: Spira
authors.affiliation: 3 Bioinformatics Platform Institut d'investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Susana G
authors.initials: SG
authors.lastname: Kalko
authors.affiliation: 1 Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain.|2 Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Madrid, Spain.|5 Respiratory Institute, Pulmonary Service, Hospital Clinic, Institut d'investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain; and.
authors.forename: Alvar
authors.initials: A
authors.lastname: Agustí
mesh_terms: D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008168:Lung; D008297:Male; D008875:Middle Aged; D011656:Pulmonary Emphysema / Q000276:immunology*
keywords: CCL19; CXCL13; inflammation; lymphoid follicles; smoking