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

Am J Respir Crit Care Med. 2016 Jun 1;193(11):1242-53. doi: 10.1164/rccm.201507-1311OC.


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.

Keywords: CCL19; CXCL13; inflammation; lymphoid follicles; smoking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • B-Lymphocytes / immunology*
  • Female
  • Gene Expression Profiling / methods*
  • Humans
  • Lung
  • Male
  • Middle Aged
  • Pulmonary Emphysema / immunology*