Network Analysis of Lung Transcriptomics Reveals a Distinct B-Cell Signature in Emphysema

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Abstract
Rationale: 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. Objectives: To explore and contrast the molecular pathogenesis of emphysema and bronchiolitis in COPD. Methods: 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. Measurements and Main Results: 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. Conclusions: 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.
Funding Information
  • Instituto de Salud Carlos III (PI12/01117)
  • Sociedad Española de Neumología y Cirugía Torácica (PI065/2013)
  • Sociedad Española de Neumología y Cirugía Torácica (PI192/2012)

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