• Rosa Faner, Tamara Cruz, Teresa Casserras, Alejandra López-Giraldo, Guillaume Noell, Ignacio Coca, Ruth Tal-Singer, Bruce Miller, Roberto Rodriguez-Roisin, Avrum Spira, Susana G Kalko, and Alvar Agustí.
• 1 Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain.
• Am. J. Respir. Crit. Care Med. 2016 Jun 1; 193 (11): 1242-53.

RationaleChronic 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.ObjectivesTo explore and contrast the molecular pathogenesis of emphysema and bronchiolitis in COPD.MethodsWe 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 ResultsWe 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.ConclusionsOur 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.

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